I'm Aware That I'm Rare: the phaware® podcast

I'm Aware That I'm Rare: the phaware® podcast is devoted to raising global pulmonary hypertension awareness with dynamic stories from PH patients, caregivers and medical professionals from around the world. Through this series of impactful, insightful and, most importantly, hopeful stories from members of the global pulmonary hypertension community, we hope to further the global #phaware conversation as well as to capture, engage and enable misdiagnosed and undiagnosed PH patients because early diagnosis and treatment can mean the difference between life and death. Topics range from the importance of early diagnosis and global PH awareness, to the impact of clinical trials to how patient support and advocacy are paramount to battling this disease. Learn more about PH at www.phaware.global

Lia Barros, DNP and Tijana Milinic, MD - phaware® interview 529 07/16/2025

Lia Barros, DNP and Tijana Milinic, MD - phaware® interview 529 Dr. Tijana Milinic and Lia Barros, DNP, from the University of Washington take a deep dive into the world of pulmonary arterial hypertension (PAH) clinical trials and discuss why diversity and inclusion matter. They explore the hidden biases in medical research and the real-world consequences of exclusion. Lia Barros, DNP: My name is Lia Barros and I'm a pulmonary vascular disease nurse practitioner specialist. I work at the University of Washington, where I've been practicing as a pulmonary vascular disease specialist for about the last four years. I was born and raised in this area. I'm really passionate about diversity and equity inclusion in clinical trials as I'm the daughter of an immigrant. This is something that I believe has affected me personally. It’s something that I see a lot professionally, that's sort of led me into this intersection of trying to understand equitable inclusion in the space of pulmonary arterial hypertension. Tijana Milinic, MD: Hi, my name is Tijana Milinic. I am a pulmonary and critical care physician here at the University of Washington in Seattle. Much of my work is as a pulmonary specialist. I also am a physician scientist. I specifically study equity and inclusion in clinical trials in pulmonary disease. I came into this work because I'm very passionate about having equal access to care for all groups of people. I, myself, am a refugee from Eastern Europe. Similarly, my background really is the reason why I have such a passion for people having access to medical therapies, and specifically new and potentially life-saving medical therapies in clinical trials. The work that Lia and I did together was the paper focusing on equity and inclusion in PAH, pulmonary arterial hypertension studies. The crux of the paper highlights that certain groups, specifically those who are ethnically and racially minoritized in the United States are not represented fairly in clinical trials. First, what do we mean by ethnically and racially minoritized people? Specifically, we're talking about individuals who have racial, ethnic, or cultural identities that have historically or presently experienced discrimination, marginalization, or unequal treatment in society. When we talk about clinical trials, we're specifically thinking about those studies that look at medications or new drugs, and evaluate whether they work or cause unintended side effects, whether they're safe and effective. Overall, what we found and what we know based on a lot of the research we've done is that clinical trials don't represent the overall population of people that will eventually end up taking a medication or therapies. In the United States, and this is generally among all disease conditions, we know for example, that over 20,000 studies done in the US, out of those only 43% included or reported race or ethnicity. Today, we'll be talking a little bit more specifically about PAH and we'll discuss a little bit about the inclusion in PAH trials, but we'll give kind of a broad view of who's included in the registry and also who's included in clinical studies. In order to understand who is included into clinical studies, we really have to have a good understanding of who has the disease overall. Specifically, for pulmonary arterial hypertension, we do that in something called disease registries. What we do know is that black African-American, Hispanic, Latinx, and indigenous communities, but more specifically for black and Hispanic communities, in pulmonary disease in general, we know that those populations experience worse health outcomes and potentially have limited access or more limited access to medical care in general. In PAH, there's some signal with small studies, for example, objective measures like how people are feeling or things like six-minute walk tests or functional status, may be worse in specifically groups that are historically ethnically or racially minoritized. When there is limited access to things like clinical studies that further worsens those already comparatively worse health outcomes. Lia Barros, DNP: If we take a step back and we think about pulmonary arterial hypertension, this is a rare and severe clinical condition that is characterized by progressive remodeling of the pulmonary vasculature. So when you are operating with a rare disease state, sometimes it becomes challenging to understand the data and demographics being an example of that across the population. Over the last several decades, there's really been a proliferation of therapies that have been approved for patients with PAH that have made really meaningful improvements in outcomes. However, little is known about the inequity in the care of patients with PAH. Even less is known about racial and equitable inclusion in participants with PAH in clinical trials. When we were preparing for this paper, what we really discovered is that we don't know. Is this something that we need to continue to explore or study? As Tijana mentioned, the way we try to understand do these clinical trials offer an equitable representation of patients living with pulmonary arterial hypertension? We went to look at these voluntary registries. We found that many of these registries did not report race or ethnicity. Several of the registries did not have patients selecting or informing how they identify with their race or ethnicity. So, there are many different challenges when trying to understand the population at large. If you go all the way back to when the first registry was published in the 1980s, this showed that patients living with PAH were predominantly young white women. This racial and ethnic impression was further reflected with subsequent registries that included the Reveal Registry, as well as the PFAR and SPHERE Registry. In general, they reported somewhere between 70% and 80% of participants reported their racial or ethnic background as white. About 10% to 15% would report identifying with black, and 9% would be Hispanic. Is this consistent with the broader range of racial and ethnic demographics within our country at large? What we found when we looked at that is that patients who were historically ethnically marginalized, were under-reported in these patient registries. What we wonder and what we reflect on is the barriers for patients to participate in voluntary registries… maybe those same barriers impact people and patient's abilities to participate in clinical trials. What happens is we get this false belief that because this representation is seen in the registries, that therefore our clinical trials do have equity in their representation. When in reality just both struggle from the same systemic barriers. Tijana Milinic, MD: When we think about the mechanisms that produce a lot of these systemic inequities, I think it's really helpful to approach it across multiple levels. What I mean by that is going from the level of the individual or person and the barriers they may experience, all the way to large systemic policy barriers, in the United States for example. All of these could equally apply to participating in a clinical trial or a drug trial and to participating in something like a registry. The first level is kind of the individual level or the level of the person, whether a person can take time off work, the cost of transportation to getting to study centers, the burden of potentially participating in a study for example. Clinical trials involve things like lab draws or more invasive procedures. Depending on what kind of study it is, could involve more barriers and more burden to participating. That also lends itself to thinking about the risks of participating. So, on an individual level, for a person living with PAH, the risks of trying a new drug could potentially outweigh the benefits of symptom relief or feeling better for example. The next level we looked at in our study was the interpersonal levels, things like how a person when they go to a study center with the study staff. When we think about participating in a trial or even in a registry, there may be a certain level of bias. Even though the person is there and has access to go to their appointments, there may be bias in whether staff thinks that they are a candidate for the study or would be willing to participate or would consistently be available to participate. That bias can be conscious or unconscious. But we know based on studies that we've done outside of PAH that that's a known barrier to people having access to studies. Along the same lines, the diversity of a study team really impacts someone's care in general, but also whether they can participate in studies. If people don't see other individuals that potentially identify with their culture or race, they're less likely to participate. Also, we actually know based on studies that when there's cultural congruency, that someone's race or ethnicity aligns with their providers, that they actually receive better medical care. That, we think, also is related to some of the biases that exist. Another similar barrier is translation services. In something like clinical drug trials, consenting is a really important part of the process. So talking about the risks of participating or the benefits and talking about really explicitly about what the drug involves or the trial involves is a really complex and difficult conversation to have. So, not having adequate translation services is yet another known barrier. One specific thing to point out is when that translation service happens. So how early on in a study also influences whether people have access to the study. Specifically, who I mean, is those who do not speak English as a primary language. Organizational and more center and study level barriers are the next level. When we think about organizational barriers, we think about things like the inclusion criteria of a study. So, whether somebody is eligible to participate depends on whether they fit the inclusion or exclusion criteria. In PAH, that's often things like six-minute walk tests or other objective clinical measures, BMP, people's functional status. When we design studies, if those criteria are too limited, then that restricts how many people can participate potentially, and could potentially restrict in a biased way who can participate. Along those same lines, the level of bias within those objective measures is also really important to think about. In pulmonary disease, in general, we think about things like the lung function. Some of the equations we use actually are biased toward the estimating lung function incorrectly among black or African-Americans. I use that as an example not specifically related to PAH, but just to think about that some of our objective measures can also be biased and influence whether somebody participates. When we design our studies, we have to think about the level of time commitment involved, whether that excludes certain groups of people because for example, they have multiple jobs or they are responsible for child care. Then, the geography of a study could potentially be restrictive. If an academic center or a PAH center is in a large city for example, that could increase the distance to travel or the commitment for people who live in more rural areas. That could potentially limit the population of people, especially if they are in a specific minoritized racial and ethnic group. On a community level, we often discuss the idea of mistrust in communities. For clinical trials specifically, there is a history of exploitation of black African-Americans and Hispanic and Latinx people in the United States. Oftentimes, people cite studies like the Tuskegee trial, but there are multiple studies where the process of consent was taken away or undue harm was caused on a population of people. That legacy has left mistrust in the medical community, but we also highlight that it's made medical research less trustworthy. That affects whether people feel comfortable to participate in medical research and even in registries where part of the risk in participating in a registry could potentially be loss of privacy of information and so on. On a broad scale, we also have to think about how national policies in the United States that don't necessarily even affect medical research, how those can disproportionately disadvantage groups of people, and therefore indirectly affect whether people can participate or are asked. It's a really complex system that operates on multiple levels, and that's what makes it really hard to study and to think about, because there's so many different levels that can affect whether somebody is asked to participate in a registry or even a trial and whether they can. That also makes the solutions difficult to address as well, because of that level of complexity. Lia Barros, DNP: Taken all together, when looking at the population of patients living with PAH, what we believe to understand is that about 20% to 30% of those patients identify as a minority, while about 70% to 80% identify as white. There could be a very cautious support that this is a good representation of the actual population living with PAH. If we look at the US census, that suggests about 71% of people in 2020 identified as white and about 65% or so percent identified as white only. So, while understanding the demographics of the PAH population at large is likely imperfect, the breakdown of what we understand could be a reasonable benchmark when we look at the clinical trials within therapies for patients with PAH, to say, are they representing the population that they're trying to serve? So, looking at PAH clinical trials, we found that the landmark study looking at epoprostenol actually did not include race or ethnicity at all within their trial. But, following the next decade or so, there were a proliferation of studies that did include this information. Time and again, what we found is that white participants seem to be overrepresented ranging anywhere from about 80% to 86% of the participants in the studies. Even looking at more contemporary trials, in the last few years, this representation continues to persist. Most specifically, I think it's important for us that we highlight that black participants are consistently underrepresented. When we talk about barriers to participation, understanding the history in America becomes important when we think about why this may be true. When we look at different clinical trials, consistently, participants who identified as black only made up anywhere from about 2% to 4% of participants in those clinical trials, which is far less than we would expect based on the US census and based on what we understand about PAH demographics at large. Tijana Milinic, MD: When we're thinking about study design, it's also important that patients are involved through the whole process. First, we actually start by evaluating what the community's needs are, whether the study that we're doing even addresses a community's needs. Specifically, this is important for minoritized communities, because historically these communities and their voices have been marginalized. Their voices, their needs, have not historically been addressed. So, community engaged research is actually a really important and powerful tool to bring patients to the table and include patients throughout the whole process. First, we start by understanding the needs of the community. Then, we incorporate and include the community into the research design process. Then, we actually bring our results back to the community and give them an idea of what we're finding and how we're doing the research so far. This allows our research to center the voices of marginalized people and people who've historically been excluded from studies, and also to ensure that our trial conduct is safe for those communities, and is welcoming. Lia Barros, DNP: I think just sort of in summary, that these inequities in PAH clinical trials are important. They're important for us to name, and they're important for us to understand. Clinical trial recruitment that doesn't represent a PAH population more broadly may impair our understanding in drug effects, may impair our understanding and understanding outcomes of treatment. I think overall, is a disservice to those we serve as clinicians. I think that from this paper, one of the things that's really hit home for both of us is that more effort needs to go into understanding who is living with PAH, and are we including those patients when studying therapies targeted for their disease. Thank you for listening. My name is Lia Barros… Tijana Milinic, MD: And I'm Tijana Milinic, and we're aware that our patients are rare. Learn more about pulmonary hypertension trials at . Engage for a cure: #phaware Share your story: Like, Subscribe and Follow us: . #phawareMD /episode/index/show/phawarepodcast/id/35538135

Episode 529 - Lia Barros, DNP and Tijana Milinic, MD 07/15/2025

Lana Melendres-Groves, MD - phaware® interview 528 07/09/2025

Lana Melendres-Groves, MD - phaware® interview 528 Dr. Lana Melendres-Groves dives into her research on racial and ethnic disparities in PAH treatment. From differences in medication access to the role of social determinants of health, she explores how systemic barriers impact care and what steps can be taken to ensure equity and inclusivity in PAH management. Hi, I am Lana Melendres-Groves. I'm at the University of New Mexico. I’m the Pulmonary Hypertension Medical Director of our Comprehensive Care Center. Today, I hope to dive into a little bit of the information that we have regarding how we care for different subgroups of our patients with pulmonary arterial hypertension. Often we are just struggling to understand the disease state and how to manage our patients. Now that we have really started to understand the disease better and have more modalities of treatments for our patients, it's really come to the forefront that there are potential differences in how we are managing different ethnicities races. So, some of the areas that I have really had a substantial amount of interest in looking into is are there differences and disparities in how we're managing patients? If so, what might those be? And how might we create more equity and inclusivity when we're talking about taking care of our patients? In today's world, we have only a little bit of information from prior studies and registries where we are able to collect information on subsets of patients such as Hispanic patients versus non-Hispanic white patients. In that specific instance, what we saw was that there might be a potential difference in the types of therapies that the patients were receiving. Then, when we look at other registries, that doesn't seem to play out the same. So, as part of some of my recent publications and research has shown, our patient populations really just need more investigation. My recent presentation on Hispanic versus non-Hispanic white patients in pulmonary arterial hypertension showed that first the claims database that we use, that our patient population that were Hispanic tended to be a younger population of patients. They tended to be of a lower economic status. They also tended to have a lower educational level. So, trying to understand if that may impact the type of care that they're receiving or what type of care they're receiving. And looking then into what medications these patients were being prescribed, how quickly after their diagnosis were they being prescribed and maybe even how many therapies at one time they would be getting as their initial therapies were of great interest to me. We were able to collect data that indicated that not just the Hispanic population, but both the Hispanic and non-Hispanic white populations actually were not receiving what we would consider the standard of care, meaning giving them combinations of therapies, knowing that that will improve outcomes in terms of how long they live and how they feel and how many hospitalizations they may have. In that situation, that brings up a completely different concern about how we are able to access medications. Are there barriers because of insurance and payers? Is it barriers because of access to follow up and management by experts? Then, when we look a little bit further into some of the results more specific to the Hispanic population, we found that what we think of as our sort of most robust medical therapy, which is a prostacyclin therapy, that they were much less likely to receive that as their initial therapy compared to their counterparts that were white. It's a great question as to why they may be identified at a younger age. Some of it is that they also tend to be more likely to have a congenital heart defect. So, that's somebody who has been living with this defect since birth. So, [the patient is] probably is presenting earlier because of that. So, that may be one component of it. We also, at least in New Mexico, see that there is a lot higher rate of connective tissue disease, which we know can be a risk factor for developing PAH. We still know that from the time of symptoms to their actual diagnosis is getting longer as opposed to recognizing those symptoms sooner and earlier and being able to diagnose it. But on the flip side, despite the Hispanic population being sort of younger at diagnosis, one of the recent posters that I presented at CHEST 2024 indicated that there was actually a substantial delay in initiation of therapies. So, comparing them to the white cohort, there was almost double in terms of the time to getting started on therapies for a first therapy and then double the time that it would take to get to a second therapy added on. And the difference, when we looked at triple therapy patients for the white population, it was about a year and a half from time of diagnosis to initiation of a third therapy. For the Hispanic population, it was three years. So, you may say they're being identified earlier because their symptoms are earlier because of other reasons, but yet they still are not being necessarily treated in the same manner. And again, a lot of the individuals, especially in the claims database would say, well, we can't assess the severity of the disease and their risk status. However, in the poster that I presented, the data that was complete looking at the risk status for those patients, they were showing that they were in an intermediate or higher risk status. Meaning that you should be adding therapies to their regimen if you're following the guidelines. So, of course, there are limitations to how we gathered this data through the claims database, which is really utilizing coding and payer information. But if it does play out that the Hispanic population is maybe not receiving prostacyclins, which tend to be a little bit more intensive in terms of care and needs, is that related to ethnicity or is that related to social determinants of health? The other thing that we found was that the Hispanic population also tended to have an increased number of other disease processes, or we call them comorbidities. So, how does that play into our management of our patients? I think that for me, the most important thing is that we recognize that there may be differences in how we are approaching management of our patients, that we try to start to understand if that's related to race, ethnicity, social determinants of health, or something else, because it's only an acknowledging and understanding that that we would be able to move forward in a more inclusive and equitable manner. What I will say is New Mexico is a minority majority state where upwards close to 40% of our population would identify as Hispanic. We also know that as of the census in the United States of 2020, we were approaching about 20% of the population in the country as being Hispanic with the anticipation that by 2050 we'll be closer to 40 to 50% Hispanic. So, even though in the current day, not every state may be the same in terms of the diversity that they experience, we are seeing that this is increasing. If we're not in a position to start understanding that now, in 25 years, we're going to be way behind. I would say that in New Mexico we face many barriers. I think my colleagues would agree frequently, there is sort of a rural population that it's more difficult to access healthcare. There are multi-generational homes where often individuals aren't able to come in to be seen due to needing to care for children or for their elders. There are also the issues with just coverage. When we look at the Hispanic population, and this has been shown on multiple occasions, is that it tends to be a younger age with which they're diagnosed as compared to the white population. Whether that means they have less access to certain types of insurances and payers, and if that could be a barrier. The continued cost of these therapies, which are very high, we're fortunate that there are a lot of opportunities for grants. But whether it could be language barriers that prevent individuals from being able to access those types of grants or understand them, as well. So for us in New Mexico, we really look to implement a multidisciplinary approach, which includes a social worker who is working directly with the patient and their caregivers to understand what those barriers might be. And how can we work with them and through those barriers to still give them the care that they deserve. So those are, I think quite a number of the barriers we are seeing. We really are diving a lot more into social determinants income and education level, and when did somebody potentially come to the United States and what is their comfort level with accessing care? So, those I think are a few things that myself and my colleagues have been attempting to get more information on. I would say that thus far in the studies that I've looked at, we haven't necessarily included drugs and toxins as sort of a specific measure. If it is captured, then it can be included, but there is a lot of missing data in terms of that. I will say that it's an area of tremendous interest and currently being looked at and studied through NIH funding. Hopefully there will be further information when it comes to methamphetamines and how that may impact potentially certain demographics of patients versus not. One of the biggest concerns that I have for any patient is that they don't feel that they have the right or ability to advocate for themselves. We also know that often, women are less likely to be able to be heard and feel empowered to ask questions of their providers, specifically if they are of a different gender. Because this is a disease that tends to affect women more predominantly than men, my recommendation is take someone with you. Make sure that you have people who support you and that you yourself can advocate. These types of podcasts and many of the other initiatives that are out there try and teach patients the information that they need to be able to then stand up and speak for themselves. That's huge, because I think that we look at PAH and in this situation, the way that we gage how severe someone's disease is in terms of how likely they're to survive for a certain period of time is often based off of what their functional exercise capacity is. That comes from what they tell me. So, there has to be transparency with your provider. You have to feel that you are being supported and that that isn't just you standing up for yourself, but the person you're going to is advocating for you as well. I think the more we can educate, the more we can advise and support these patients and anyone caring for these patients is the way that we move this forward. I think that research and clinical trials are tremendously important. I will say that when I started the Pulmonary Hypertension program at UNM back in 2012, I was not per se what you would consider a research oriented clinician. I really was all about taking care of the patient feet on the ground, managing those patients until I recognized that if I wasn't working to provide opportunities to expand our knowledge and include my patient population in research studies, that I really wasn't doing everything I could for my community. So with that, it took go and learn, really becoming a researcher, because that's what the patients deserve. They should get to choose if they wanted to be part of a clinical trial, it shouldn't be because they couldn't be part of a clinical trial because it wasn't offered. One of the things at UNM that we have work to do is to build into the budget of our trials for being able to translate all consents into Spanish. So that isn't a barrier that if you speak English, you speak Spanish, you still have an opportunity to participate if you want. To make sure that our research coordinators, that we have someone who is bilingual so that they can actually communicate in their own language with the patient without those types of barriers, because we know that that excludes people. I think that those are areas in terms of research and clinical trials that we need to do better, but we also just have to present it to patients. I think there's still a sense that maybe somebody is not getting the best care because they're being treated as a subject, but in reality, I think that I know my patients receive more care, more touch points, opportunities to be able to be heard, speak up, and then be included in the overall results so we understand better how to care for that population. Maybe it's no different, but if we don't have that cohort in the clinical trial, then we would never know. If we are not including these patients in our clinical trials and our research that we'll never understand how best to care for them. One other piece that I would say is that we continue to look at our management of PAH patients. Even though our guidelines and the recommendations coming out from not only the United States, but our European cohorts say combination therapy, potentially triple therapy treat until someone's risk status is low. If that means they need three or four medications, that's what we should do. We still continue to see that patients are under treated and that we are not managing them despite knowing the information in terms of improved outcomes if we manage them appropriately. I think we ourselves, as the clinicians, continue to need to reassess how we're managing our patients and maybe why we aren't giving them more therapies. Thanks so much for listening. My name is Dr. Lana Melendres-Groves, and I'm aware that my patients are rare. Learn more about pulmonary hypertension trials at . Engage for a cure: #phaware Share your story: Like, Subscribe and Follow us: . #phawareMD /episode/index/show/phawarepodcast/id/35538235

Episode 528 - Lana Melendres-Groves, MD 07/08/2025

Roham Zamanian, MD, FCCP - phaware® interview 527 07/02/2025

Roham Zamanian, MD, FCCP - phaware® interview 527 Dr. Roham Zamanian, discusses the concept of "disease modification" in the treatment of pulmonary hypertension. He describes how this idea emerged from discussions with colleagues about the future of pulmonary hypertension therapies, and the potential for treatments to impact the underlying disease process beyond just reducing pulmonary artery pressures. This Special Edition Episode Sponsored by: My name is Roham Zamanian, and I'm the Medical Director of the Adult Pulmonary Hypertension Program at Stanford. Today, I want to talk about disease modification, something that historically, probably is not on the radar of the work that we were doing, but now, because of advents of new therapies, is a concept that we should be discussing. It's a concept that people have talked about in the last couple of years. It became a with a PH patient involved, that received some traction during the World Symposium on Pulmonary Hypertension. Like a lot of concepts in research and pulmonary vascular disease, concepts come up in discussion with colleagues. I remember sitting in Barcelona with Vinicio de Jesus Perez, MD and Harm Bogaard, MD. This was probably 2019. We were talking about the next phase of what's coming up in pulmonary hypertension research. The two concepts that sort of came together was this idea of doing a large sort of efficient clinical trial using something called the master protocol. Then, the conversation led to, well, what's the future of therapies in pulmonary hypertension and what are the hopes that we have for these therapies? A lot of us are not naive enough to say, "Well, we want a cure." We certainly do, but are we there yet? We're not sure. But we were talking about therapies that are on the horizon, being tested in animal models and being spoken about in clinical trials that have the potential for changing the vasculature or really impacting the disease in a way that is significant. When you look into medicine around therapies that have that kind of capacity, you get conversations around anti-immune therapies that what were called DMARD, disease modifying anti-rheumatic drugs. Then, it was like a light bulb sitting at this cafe in Barcelona. Before we knew it, we were talking about, "Well, what does the concept of disease modification look like in pulmonary hypertension?" Are we there yet? Do the drugs that we have now modify the disease? We realized very quickly we didn't have consensus around that definition. To all of us, disease modification or changing the disease in a way that was substantial, but short of a cure meant different things to all of us. To some people it was like, "Hey, let's take the blood vessels of the lungs and reduce occlusion and the new intimal changes from a pathology perspective." To others, it was like, "Yeah, I care about that, but I also care about what's happening to the right heart." To others it was like, "Well, how does the patient feel about this?" So that conversation began. I don't think we're the only ones in the community having these kind of conversations, because we're realizing now that these therapies that are coming out have the potential to address the underlying mechanism in a way that's just beyond vasodilatation. We felt like there was a need to have this conversation across our community, and that's what led to the paper. Initially, it was like, let's figure out what the outline of conceptualizing this phrase is. What does it mean to all of us? How do we measure it? How do we test it? That's the main thing. We are trying to also police ourselves and the community and how that term is being used. We're getting this group together and we said there's two important things that we need to have. We need to have a perspective from someone who has experience from a regulatory perspective. We ought to test this concept. So we need someone who has know-how knowledge experience with part of EMA or FDA or whatever. The second thing was, it's imperative that we have the patient voice in this conversation, because the kind of maneuvers that we're thinking about and we proposed in our manuscript will require feedback from patient community, because they'll be in those clinical trials. I have a patient of mine who is a dear patient of mine who is a physician, also. I thought that was really great, because then we would have someone with medical knowledge involved. We engaged her. She blew us away. If you look at the paper, you'll see, we talk about what is the definition of this concept, how do we approach it and how we think about it medically. She was like, "Hey guys, I don't care. What I care about is how does that feel to me." That was really sobering. In fact, I want to give a shout-out to the , the Blue Journal. We basically said, "Here's a section of what the patient said. We're not going to make it into Medicalese. It's going to read like a first-person what the patient is telling you." And they allowed us to put that in. This is the first time that this medical journal, for me at least, allows really the voice of the patient speaking through all the medical jargon of the paper. I think it's really important because one of the critical items I believe, and this is an opinion, to test this idea of whether a drug is modifying the disease, is to test withdrawing the drug for a period of time to see how much effect it has had. If I could biopsy your pulmonary arteries to say how much reduction in vascular remodeling there's been or biopsy your right heart on a routine basis, we would do that. Those are not easy maneuvers. Those are not without risk. No one ever biopsies the pulmonary arteries. Short of that, we strongly believe in this manuscript, we wrote this, that we can't just because the drug works really well, we can't say that that drug is changing the disease at a pathology level reversing it, because we don't have evidence of that. So our manuscript calls for ways to test it. One of the cornerstones of testing get is to withdraw the drug. The patients have a very strong opinion about what that means, and we have to be careful about explaining that construct carefully enough in a clinical trial setting. So, it was really important to have the voice of that patient in a manuscript. Just to be fully transparent, there are other manuscripts that are being published or have been published. I'm not sure if they're out yet or not by other colleagues, and they may say similar things to us or different things to us, but the reality of it is, it was not part of the clinical trial. Now, we think the idea should be tested in the clinical trial. We know, and we're very strong in the opinion that just because a drug can be very impactful in reducing pulmonary artery pressures, it doesn't mean that it is somehow changing the underlying pathology of the disease. For example, Flolan, (Epoprostenol), life-saving drug, has profound ability to reduce pulmonary artery pressures, but in the long term, it doesn't change the disease pathology, doesn't change the fact that patients end up needing a heart-lung transplant. Hopefully they never do. In our thinking, this idea was to really outline how we think about a term that shouldn't be used willy nilly and a concept that should be tested in clinical trials. As this concept gets air and people were discussing it at the World Symposium on Pulmonary Hypertension through our task force, which was the clinical trial's task force. But in the broader sense, how it fits into the community, I think there are different opinions. I think generally people see this as a good concept to understand and people I think do agree now that we should be testing it. We're at a place in PH that we could test it. Most people are sensitive to the idea of withdrawing a drug. I'll tell you in a very simple way, first of all, we're no longer at a place where there isn’t experience managing patients on already background therapies. We're talking about in the setting of a clinical trial, right? We're not saying that someone should test this in clinical practice. In clinical trial, all clinical trials now require patients to be on background therapy, require patients to be closely monitored. So, I think it is the right environment to take a patient through a period of time where you take the drug off and see how patients do. I think people are open to it, but we always have to start with the primary construct. A lot of patients, and even some physicians I think have reluctance about this concept or may have reluctance around this concept, because they feel that the drug that they're getting, and maybe they're already on it or they're on placebo, who knows? Right? Is going to be effective. But that's what the clinical trial is testing. So it doesn't mean we're asking patients to withdraw immediately from an effective drug. We're asking them, at least in our manuscript, we ask that whether the drug that's being tested, before it's proven to be effective, is withdrawn during a period of time and evaluated for this idea of disease modification. There are people in this field that think you could also withdraw background therapies, so they go on a drug. If that drug is really helping them substantially, then you should be able to take away some other already approved background therapy drug that are on. There are different permutations to it, but that's been the entirety of the discussion. The biggest point of the discussion has been can this be safe and tolerable for patients to do in a clinical trial? I think a lot of people believe it is. In this day and age of pulmonary hypertension care, it's viable. Then, the second part of it is what signals do we look at to say something is disease modifying or not? What are the, if you will, endpoints? Is it the six-minute walk distance? Is it the PVR? Is it some surrogates of the PVR? Is it blood tests? What is it that we're looking at? I think there is going to be a lot of exciting innovation in that front that people can look forward to. But that's been the discussions both at around the World Symposium on Pulmonary Hypertension. I know we're going to talk about this at the PVRI meeting in Brazil. I'm sure people are talking about it either at regular conferences or between themselves, but it's exciting. I've been in this field since the early 2000s and it's exciting to be in a place in time where we can think about testing something like this. It feels like progress to be even in a position to test it. I'm Roham Zamanian and I'm aware that my patients are rare. Learn more about pulmonary hypertension trials at . Follow us on social @phaware Engage for a cure: #phaware Share your story: #phawareMD /episode/index/show/phawarepodcast/id/34897155

Episode 527 - Roham Zamanian, MD, FCCP 07/01/2025

Hall Skaara - phaware® interview 526 06/25/2025

Hall Skaara - phaware® interview 526 Hall Skaara, representing PHA Europe, brought to the forefront at the World Symposium on Pulmonary Hypertension, joining other members of Task Force 1. PHA Europe was well-represented with delegates including Eva Otter, Monika Tschida, Natalia Maeva, Tadeja Ravnik, and Nina Kobler. This prestigious event gathered over 1,500 of the brightest minds in the field of pulmonary hypertension, offering a unique opportunity for patients and professionals to collaborate and share insights, as well as for patient associations to network. This Special Edition Episode Sponsored by: My name is Hall Skaara. I'm Norwegian. I was diagnosed with pulmonary hypertension back in 2005. It's actually been 19 years living with this disease. I'm doing quite well. I'm still on monotherapy. I started the Norwegian (Pulmonary Hypertension) Association because there were no associations in Norway. We became part of PHA Europe. I started getting more involved with the PHA Europe work and somebody else took over the Norwegian Association. I've done a lot of tasks with PHA Europe. One of the most interesting things I've participated in was being part of a task force for the . I don't know if everyone is familiar with what the symposium is, but this was initiated in Geneva in 1973. There were only 13 participants at this first meeting. Their key objective was simply to understand the basics of PH. Then, the next time they met was in 1998. Then, they met in five years intervals up until 2024. The key objectives have changed somewhat now. Now, it's more to promote knowledge exchange by sharing the latest research and clinical advances, promote collaboration and networking, update and development of guidelines, educate healthcare providers and stakeholders, and raise awareness for PH. During this last seventh symposium, there were approximately 1700 participants. I had the pleasure of being part of one of these task forces. They divide things into working groups. They had 15 working groups. In 2018, it was the first time that patients were involved in this work. They were the last task force and the last to present. I think many had left the conference area at the time. So, they did something different this time. They let the patient task force be number one. We had the pleasure of opening this conference. I think this was very fitting. It showed their willingness to let the patient be in the center. For me, it was a great thrill. I was one of the presenters. My son sent me a video of him bungee jumping. I thought, "I've never done stuff like that. But what I've done is that I've talked in front of 1700 specialists." Our work resulted in this presentation at the symposium, but also in some proceedings. These proceedings were published in the on August 29th, 2024. Anyone that wants to have a look at that could go into the journal and read not only our proceedings, but also the proceedings from the 14 other task forces. We had four doctors on our task force. It was Jimmy Ford, Simon Gibbs, Adam Torbicki and Victor Moles. We had two patients. It was me and Colleen Brunetti from PHA in America, and one former patient who has gone through a double lung transplant, Pisana Ferrari. Then, a patient advocate, Gergely Meszaros. We shared our presentation with Colleen. Her main thing was “no decision about us without us.” She also talked about how it was for her personally to live with PH. Then, Adam talked about the past of the patient associations, how things started in the US around the kitchen table, and also the start of PHA Europe. One of the first questionnaires where they talked to patients about quality of life and life expectancy. Even at that point, many, many years ago, they talked about how the patients, instead of living longer, they wanted to live with better quality of life. But I guess all people are different. I want to live as long as possible, so maybe I feel a little different than other patients. Then, Jimmy talked about the global assessment of patient priorities. He started with a great quote. I think he said, "The good physicians treat the disease, the great physicians treat the patients who have the disease." We talked about how the patients, they need expert, multidisciplinary teams, proper diagnosis, access to medication, and a patient-centric approach. One thing we have done in this task force is also we have collaborated with teams around the world. A small team of global patients and providers. We gave them a survey to learn about the situation of PH care around the world. It was very interesting to get their feedback, because often we are very centered around the US and Europe. Here, we got more feedback on PH care all over the world. One of the things they talked about was that in many places they don't have enough expert centers. They have also poor access to right heart catheterization. As we know, if you don't have right heart catheterization, you don't really have a proper diagnosis. They have lack of medication in many places. In many countries you have a lack of transplant options. Also, a lack of rehab centers. What we see, also, is that there is a big difference between global south and global north. This is something that needs to be handled in the future. Jimmy talked about one way of handling this is that we have more cross border collaboration. PVRI recently had a survey with about 3,500 responders from all over the world, from 88 countries, actually. They point out many of the same things that these experts that we talked to also pointed out. Then, Pisana talked about the patient associations and how we have come a long way since the beginning. How they are much more professional and structured now than before, but we still work on some of the same things for instance awareness. We have the World PH Day on May 5th. We have the Awareness Month in November, Rare Disease Day on February 29th. Of course, also work like phaware, creating a lot of awareness for PH. We are also involved in advocacy in a totally different way now than before. We are part of steering committees in trials, working together with the regulatory authorities, etc. Also, for the first time in 2022, patients were invited to take part of the PH guidelines. We expect that this will also happen for the next guidelines that will come out soon. Then, Simon Gibbs, and I, talked about the importance of PROMs, Patient Reported Outcome Measures. These are just simply surveys that patients fill out before go into the doctor. It facilitates the dialogue between the doctor and the patient. Shared decision making will be much easier when you use PROMs. There has been a change also in this. In 2011, 20 European expert centers reported that about 20% of them used PROMs. In 2022, about 65% of them used PROMs. I talked about how I use PROMs. Actually, I developed my own PROMs to kind of track my disease. By doing this, I can see if I was too active or not active enough and how my activity level and other things influenced my disease. I think this might actually be one of the reasons that I’ve lived so long with this disease. Also, surveys have shown that if you use PROMs, then the patient’s satisfaction will increase. Also, you can use PROMs to identify risk factors. As I said, with PROMs then you have shared decision making. You enable this in a much better way than if PROMs are not used. Then, we talked about future directions. This was Gergely that talked about this. He talked about that in the future, I think we will see more and more that patients are regarded as partners to healthcare providers. He talked about collaboration with all stakeholders. I think when you introduce patients into committees and to trials into work that normally have been reserved only for healthcare providers, you eventually drive the designs forward. You enable what patients regard as important to be in the forefront of all the work you do. Patients involvement is really important in all aspects. Of course, this also puts a burden on us as patients or requirements. We need to empower ourselves in order to be able to take part in discussions. I think this will benefit the entire industry and also patient PH care, of course. You don't ask to be part of any committees. They come and ask you. It's a great honor to be asked to be part of this work, because we know that this work is very important. It's a great honor, but also a great responsibility, because I will be talking on behalf of a lot of other patients. But this is the good thing about having this disease and living with it for 19 years. I know how it is to live with it. I know what the priorities are and I know how other patients feel. It's not so difficult for me to tell what the important things are for other patients and to be their voice, to put it that way. We get great feedback whenever we as patients talk to HCPs and also the pharma industry. The feedback is always very good. I liked the feeling of standing on stage and looking out at the audience, because you just see open faces everywhere and people are very open to your message. I remember talking to a person and he said as a patient, you can really say nothing wrong, because everything you say is right. This is how it feels like to be a patient. I think also we are welcomed into this community. I think, also, it's a process that once you start and once you start to involve patients in this type of work, there is no going back. The patients will just continue getting more and more involved in all aspects of PH care. I'm optimistic on behalf of the patients, first of all, because we see medical advances and now we see kind of a new era of PH medication. We understand that as the year goes by, we will have better and better medication. Hopefully, in not too long, it will be a disease that will be manageable. Also, I have great hope for the patients being more and more involved in the different aspects of the science, the trials, committees, regulatory authorities -- in all my aspects of PH. My name is Hall Skaara, and I'm aware that I'm rare. Learn more about pulmonary hypertension trials at . Follow us on social @phaware Engage for a cure: #phaware Share your story: /episode/index/show/phawarepodcast/id/34698030

Episode 526 - Hall Skaara 06/24/2025

Lisa Mielniczuk, MD - phaware® interview 525 06/18/2025

Lisa Mielniczuk, MD - phaware® interview 525 Why Pulmonary Hypertension Isn’t Just a Lung ProblemCardiologist Dr. Lisa Mielniczuk from the Mayo Clinic pulls back the curtain on one of the most common — yet misunderstood — forms of pulmonary hypertension: the kind caused by left heart disease. In this episode, she explains why it’s time we stop thinking of PH as a rare condition. My name's Lisa Mielniczuk. I'm a cardiologist and I work at the Mayo Clinic in Rochester, Minnesota. I've been working in the field of PH now for almost 20 years. I also work in the field of advanced heart failure and heart transplantation. I've been connected in PH through my activities both inside and outside of the hospital. I've been involved in research in pulmonary hypertension. I've also been working with some great organizations like the Pulmonary Hypertension Association of Canada and PHA, as well. It's just been an outstanding opportunity for me to learn from other people to contribute to both clinical care and research. I'm here today to talk about the most common type of pulmonary hypertension that our patients are getting diagnosed with, and that's pulmonary hypertension, secondary to underlying left heart disease. Now, for those of you that know, and I think many people do know that are listening, pulmonary hypertension in and of itself is not a diagnosis, it's a classification of different types of diseases. I often tell my patients pulmonary hypertension is caused by high blood pressure in the blood vessels that are connecting the heart to the lungs. There's many, many reasons for that. As clinicians looking after our patients, it's our job to figure out if patients have pulmonary hypertension, why they have pulmonary hypertension. Because the treatments are very unique to the different causes. One of the most common causes of pulmonary hypertension is that that occurs from underlying what we call left heart disease. The left heart disease refers to the left ventricle. There are basically four main chambers in the heart. We sort of arbitrarily define them as the left side and the right side. The job of the left side of the heart is to pump all that nice oxygen rich blood into our body. The left side of the heart is often thought of as the workhorse of the heart, because it operates under high pressure and volume. Even when we're just sitting here, you and I right now, we might be pumping five or six liters of blood every minute through that left side of the heart. So it works hard for us all the time. Unfortunately, there can be different diseases that affect the functioning of the left side of the heart. When that happens, patients can develop pulmonary hypertension. There are many, many causes of pulmonary hypertension from underlying left heart disease. Those could include problems with your heart valves. It could include problems with too much stiffness in the heart. Or problems with weakness of the heart muscle function. Anytime that happens, the pressure builds up inside the left side of the heart and that pressure buildup is transmitted backwards to the top chamber of the left side of the heart, and then it can be transmitted backwards even further to those blood vessels. If that pressure is there for a long time, changes in the blood vessels can occur. You can get high blood pressure there, you can get remodeling of those blood vessels and people get pulmonary hypertension. What does that mean for our patients? It means that they feel short of breath and they often feel most short of breath early on when they're starting to exercise or do physical activity. Because when we start to exercise, work harder, move our heart more, those pressures build up faster and they get into our lungs and we feel short of breath. This is a very common condition. As I said, patients often feel short of breath. They can have some chest discomfort. They can sometimes feel very tired and sometimes develop the signs and symptoms of heart failure. I always say to folks, heart failure is a terrible term because it doesn't necessarily mean the heart has failed completely, but what it means is the heart is unable to meet the needs of our body, essentially a supply-demand mismatch. When that happens, we feel those symptoms of shortness of breath, tired, sometimes fluid retention, sometimes chest discomfort. One of the most important things I think to talk about, and one of the most exciting things to talk about is how do we treat pulmonary hypertension that is due to an underlying process that is affecting the left side of the heart? Our understanding of this problem has changed so dramatically over the last 10 or 15 years. You might be surprised to know that 20 years ago, we didn't even have a classification system to really try to understand patients who develop pulmonary hypertension from left heart disease, even though it's been known about for 50, 60, 70 years in people with rheumatic heart disease, et cetera. But we just didn't know how to describe it and we certainly didn't know how to treat it. I'd say there's been some very significant advancements over the last 10 years in this field. Historically, we've thought of the treatment of this in really two prongs. The first is, and most importantly, we want to do everything we can to improve that heart function. I'm going to talk in a minute a little bit about what those treatments might be. But in the same token, we have done many clinical trials to look and see if some of the treatments that we use for what we call Group I pulmonary hypertension or pulmonary arterial hypertension might actually work in patients who have what we call Group II pulmonary hypertension or this type we're talking about today, which is pulmonary hypertension due to left heart disease. Let's talk a little bit about the first part. How do we treat underlying left heart disease? Well, obviously it really depends on the cause, right? If you have a significant valve problem, the treatment is often to fix the valve. If your heart muscle is weak, there are great therapies that can help to improve the function of the heart. In the last couple of years, there's been some really nice developments on that field. One of those medications that has been shown to have great promise in people with left heart disease is a medication known as a class of medications called SGLT-2 inhibitors. Now, these medications, and you may have heard of them before, have traditionally been used to treat patients with diabetes. Then, over time, it was shown that if patients with diabetes had these medications, you could prevent heart failure. Then, they move the needle further, and they studied them in patients with heart failure and they found, my goodness, these medications can actually treat heart failure and improve people's outcomes when they're used, even if you don't have diabetes. The way this drug works does a lot of things that could potentially help patients with pulmonary hypertension and left heart disease. It helps to relax the heart. It helps to get rid of that pressure or fluid buildup inside our body. It helps the kidneys. We also believe that it might actually help to improve both the right side of the heart and the blood vessels that we're talking about today that are connecting the heart to the lungs. This is a really important medication now that is offered to patients who have a diagnosis of heart failure, whether or not they have pulmonary hypertension. That's one exciting development, which is new. I think when we think about pulmonary hypertension from left heart disease, one of the most common things that we see very often is that the left side of the heart gets stiff. There are many things that can stiffen up the left side of the heart. It happens more frequently as we get older. It is particularly a condition that happens more often in women than men. It can create substantial exercise intolerance, shortness of breath and fluid retention. There haven't really been a lot of treatments for people who have this sort of stiffness of the left side of their heart. Many people who get this stiffness in the left side of their heart get pulmonary hypertension. If you ask me, "How often does that happen?" Interestingly enough, we don't have a good answer because it depends on who we sample and how we define it. But based on clinical studies and registries, this could happen anywhere from 30 to 80 percent of the time, a very, very common condition. Pulmonary hypertension from left heart disease is a common condition. It's not rare. Pulmonary hypertension from left heart disease, from left heart stiffness is a very, very common condition and consequence of people who have this left stiffness of their heart. As I said, we didn't have very good treatments up until a few years ago. But now we know that this class of drugs, these SGLT-2 inhibitors, they work really, really well for patients who have stiffness of the left side of the heart. We believe now that this is the standard of care for patients who have a diagnosis of heart failure with this, what we call preserved ejection fraction or stiffness in the left side of the heart. Many of these patients will have pulmonary hypertension. But the needle doesn't stop there. There are other classes of medications that are moving forward that can really help patients who have this very common type of pulmonary hypertension. One thing we've also noticed is that there is a real link or association between obesity, having a higher body weight, and developing this stiffness on the left side of the heart. Obesity and the excess body weight we carry does a lot of things that actually can increase our risk of heart failure. It increases the inflammation and stiffness in our body and creates a lot of downstream consequences. I'm sure many of us have heard of the class of medications called GLP receptor agonists. They're always being advertised all over the TV and radio. I don't think I can drive a day in my car and not hear about them. But they're very, very exciting medications. Again, these medications were used in people who had issues with weight and diabetes, and they demonstrated significant benefit. Now, there's been two very, very promising what we call landmark trials where these class of medications were used to treat patients who had this stiffness of the heart, so heart failure with preserved ejection fraction, plus they had a BMI over 30. So they were obese by our sort of characteristic definitions. What they found is that these medications helped people feel better, their quality of life improved, their exercise tolerance improved, and yes, they did lose weight and it made a substantial impact on their overall well-being. Here's another class of medications that I think is just coming around the corner for our patients with pulmonary hypertension and left heart disease, because the incidence of obesity in this patient population is at least 30 or 40 percent. That's fantastic. The third class of medications, which I think are coming right around the corner as well, are medications that people may also be familiar with. You may have heard of drugs like Spironolactone or eplerenone. These drugs belong under an umbrella of a class of medications called mineralocorticoid receptor antagonists. Many people may be on them because they can be used for diuretic properties. They can help us to get rid of the extra water in our body. But there's also new data now that shows that these drugs can help reduce the risk of us developing worsening heart failure events if we have this heart failure from stiffness of the left side of the heart. So, therein is three brand new classes of medications that have all just come to the forefront in the last, I would say, two to five years. We now have good, good, good solid evidence that this should be the standard of care. In the span of, I'm going to say 15 years, we've gone from having essentially no treatments for patients with pulmonary hypertension from left heart disease caused by stiffness of the left side of the heart, to three very powerful evidence-based medicines. I think it is a time to be encouraged that we're moving the needle forward. The last thing I'll say about the treatments, and I've talked a lot about their effect on patients who have a diagnosis of heart failure with preserved ejection fraction. These drugs have not yet been studied specifically in our patients with pulmonary hypertension and left heart disease. But like I said, many, many patients with left-sided heart disease like this will have some degree of pulmonary hypertension. The postulated mechanisms of these medications is very favorable, that many of the ways that these drugs work would really help our patients with PH and left heart disease. So, to summarize, where we are in 2025 is a really exciting place. We have brand new treatments that can be used and should be used for our patients with pulmonary hypertension and left heart disease. I think we very much understand that this is a common condition. It is not rare. The global estimates are that if you're over 65, probably 10% of people have some degree of pulmonary hypertension from left heart disease. That's how common this condition is. And that the most common type of PH in left heart disease we see is that stiffness that we talk about, or heart failure caused by stiffness on the left side of the heart. We now have treatment recommendations, in addition, to all the other non-treatment, non-pharmacologic recommendations we have about blood pressure control, activities, salt and fluid restriction, and all those really important other things that we can do to help to keep ourselves well. That's where we are in the pharmacology. There's one other quick thing I'll say, which is I think it's just an example of how quickly the needle moves forward in medicine, particularly how fast the field is evolving in pulmonary hypertension. In addition to these medication treatments, there are also non-pharmacologic treatments that are coming up around the corner that are showing some promise in patients with pulmonary hypertension and left heart disease. Now, these are not ready for prime time by any means, but in small clinical studies, there's been some really promising evidence to show that things like nerve ablation can help reduce the inside the heart and help people feel better. And different types of minor procedures that can help to reduce pressures either through stimulating nerves, which relax our heart, or inhibiting nerves, which excite our heart, or even creating small shunts to help offload fluid from one place to another. So, stay tuned because there may very well be a whole discussion about the non-pharmacologic treatments of PH and left heart disease in the next few years. My name's Lisa Mielniczuk and I am aware that I'm rare. Learn more about pulmonary hypertension trials at . Follow us on social @phaware Engage for a cure: #phaware Share your story: #phawareMD /episode/index/show/phawarepodcast/id/36413515

Episode 525 - Lisa Mielniczuk, MD 06/17/2025

Jason Weatherald, MD - phaware® interview 524 06/11/2025

Jason Weatherald, MD - phaware® interview 524 Beyond the Clinical Trial: What Real-World Data Means for You. Think only people in clinical trials help advance medicine? Think again. Dr. Jason Weatherald explains how your everyday clinic visits - from walk tests to how you feel - can help shape the future of pulmonary hypertension treatment. Learn what "real-world evidence" is and why your story matters more than you think. I'm Jason Weatherald, I'm from the University of Alberta in Edmonton in Canada. I'm a clinical researcher, I focus on pulmonary hypertension and also on lung transplantation in my practice. I do a lot of research related to patient-oriented ideas and clinical trials. Today I want to talk a little bit about real-world data and real-world evidence and what that means, and why it's relevant in pulmonary hypertension. Real-world data and real-world evidence are related to complementing clinical trials. The way that new treatments get to the marketplace for any disease is through randomized controlled trials. These have to be approved by regulatory bodies, like for instance, the FDA in the United States, or the EMA in Europe. Clinical trials are different than what happens in the real world. When you're running a clinical trial to get a new treatment approved, you want your trial to be successful. The trial has very strict criteria on what type of people can be in it, and they have very strict measurement, and it's very tightly regulated. That's important and that's really good. That's how we know things work under ideal circumstances. However, when a treatment is approved and it starts getting used in the real world, the types of patients that are on a drug or on a device are always different than what's in the clinical trial. We call that real-world populations. So, we also need data and evidence from real-world populations as to how a treatment is actually working in practice. Because the selection criteria for a clinical trial are so narrow and so tight, the results are not always generalizable to the everyday patient in front of you who may be older, who may have other comorbid conditions. They may have a bit of kidney failure, they may be overweight, and sometimes clinical trials don't include those people. So we need other sources of knowing that a drug is safe and also likely to work in the broader population. We call that real-world data. The information that we get from real-world data becomes real-world evidence. That's the type of evidence that we can use to make decisions in clinical practice. Patient reported outcomes can still be used in a clinical trial. Those are any sort of description of how a patient's feeling or their quality of life. It's just what the patients are telling you is going on that can be used in a clinical trial. There are other types of real-world data. I'll give a few examples of what we're talking about with real-world data. After a drug is approved, now most of the regulatory bodies require companies to perform drug registries. These are basically people who are on the drug in the real world and they're collecting information about side effects, because they can look at much larger populations of people who are taking a drug. Maybe rare side effects didn't show up in a clinical trial because there's only 300 or 400 people in the trial. But what happens when 5,000 people are on a drug? So drug registries are one type of real-world data. There's also really powerful other sources that are collected in everyday practice. When you go to the hospital, you might have an electronic medical record, and then physicians and surgeons apply billing codes for all of the services that they provide. That data go to massive databases. So for instance, in the US, the Veterans Affairs has this massive database of people that have sought care, and you can also obtain data from those sources. We call them administrative databases. They may have tens of thousands of patients. You can look at associations and you can try to understand rare side effects or health resource use in the real-world population. So those can be a great source. Patient biometric data is one potential source of real-world data in the future. So you could think about a watch or a Fitbit or an Apple device collecting patients' real-world data on what's happening to them with their step counts, their heart rate in the real world. That is one other potential source that we really haven't capitalized on quite yet in the pulmonary hypertension world. But this has been used in clinical trials already, and it has been used in real-world studies in other diseases in the cardiovascular arena. I think this is one potential area, and you could even consider integrating things like your step count, your heart rate, and your patient-reported outcomes like how do you feel on a given day, multiple days in a month? Using emerging, very sophisticated computer and artificial intelligence approaches, you can get a better picture of how someone's doing day to day from that type of data that might be much more powerful than what we're collecting in clinic visits that are every three or four months apart. Those are just snapshots, and that type of real-world data is more like a videotape. It tells you what's going on all the time. For instance, like administrative databases. I've worked with this in my own healthcare region, and it's all de-identified, it's associated with numbers that could be identified. But when you get the data from, for instance, your health region or your hospital, it has all the identifiers taken out. But it may have things like age, and sex, and sort of how many comorbidities a patient has. The administrative data is de-identified, and it may be under the jurisdiction of a hospital or in Canada where I live in a province, but the drug registries are different. Participants would only get their data into that type of a setting through a normal informed consent process. They would have to sign a consent form to have their data collected. Of course, it is always under the protection of the physicians that are running those studies, and the anonymity and confidentiality of that data is the responsibility of those doctors. None of that identifiable information should be shared with the companies that are asked to run these studies. But it really depends on the setting. One of the things I hear from patients all the time is that they want to participate in research, but maybe they don't want to be in a clinical trial or maybe they don't qualify for clinical trials. This is a way that patients can participate and there's really nothing else that's asked of them. Usually, these drug registries are done as part of routine care. We're only sharing information like, how does a patient feel? What was their walk test? What was their blood test that day? If they have a heart catheterization, what are those numbers? It's a way that patients can feel that they're contributing to knowledge without having to do a bunch of extra things. For many people that's enough. They feel like they're altruistic in some senses, it's people helping the generation of knowledge in a way that they can. The other benefits I think are so that we do learn, how safe are these new treatments? How well do they work in the real world? As researchers, we can ask scientific questions that we can look at the data once it's accumulated over many years to say like, "Well, have you thought about this?" So we can even go to the companies and say, "Well, you should look at this. We're seeing this in the real world. Maybe you should make sure that this isn't the problem." For instance, risks of bleeding or risks of headaches. We might be seeing stuff that wasn't necessarily picked up in a clinical trial, and that can be a red flag that makes us do things differently to protect the safety of patients. There are lots of opportunities to tell patients about different ways they can be involved in research. It really does depend on the individual patient. For instance, at my university, we may be running five or six clinical trials at once, and the criteria for them are different. So we have a cheat sheet and we look at the patient. We always ask them, first of all, "Are you interested in participating?" If not, then the conversation ends there. But if patients are interested and they want to hear more, we do have to spend a bit of time looking at what they would qualify for. For instance, some of these drug registries are only applicable for people who are about to start a new drug. So they're starting drug A, and there's a registry for drug A. It doesn't mean that I would put them in the registry for drug B. So those opportunities only come out often when people are starting new treatments, so they may be few and far between. In terms of clinical trials, it's something I bring up almost every visit and just say like, "Hey, these are the opportunities. Do you want to participate?" If not, we end it there. But people change over time, they might not be eligible for a clinical trial at this visit, but maybe in six months they are because things have changed, or maybe they're not on a certain drug that's excluded, or maybe they're a bit worse and now they qualify for clinical trials. It always adds extra time to the visits, but it's important, I think. One thing I always say is that all of the treatments we have now are only here because of people who participated in trials in the past. Some of those people are no longer with us. That's their legacy, That's the gift of knowledge that they gave to the future generation of people with PH is we learned what works and what doesn't work because of people that participated in trials. I think that's important that people understand that, and acknowledging that it's still not right for everybody to participate in a clinical trial. But what I like about the real world data is that that's just a great example of how people can contribute in other ways. There's other registries. A lot of countries have national registries where patients can sign up. Again, we just collect data from each visit as people come through the clinic, it's just reflecting what happens in the real world, and that's where the name comes from. I'm Dr. Jason Weatherald, and I'm aware that my patients are rare. Learn more about pulmonary hypertension trials at . Follow us on social @phaware Engage for a cure: #phaware Share your story: #phawareMD /episode/index/show/phawarepodcast/id/36413620

Episode 524 - Dr. Jason Weatherald 06/10/2025

Rodolfo Estrada, MD - phaware® interview 523 06/04/2025

Rodolfo Estrada, MD - phaware® interview 523 Dr. Rodolfo Estrada, is a seasoned pulmonologists currently at UT Health San Antonio with significant experience in the management of patients with different forms of pulmonary hypertension. In this episode, Dr. Estrada will discuss the technology and clinical development behind YUTREPIA™ (treprostinil) inhalation powder and why it might be a good option for some PAH and PH-ILD patients. This Special Edition episode is sponsored by . Please see the Important Safety Information following this podcast. The Prescribing Information and Instructions for Use for YUTREPIA (treprostinil) inhalation powder are available at YUTREPIA is approved for the treatment of pulmonary arterial hypertension (PAH; WHO Group 1) and pulmonary hypertension associated with interstitial lung disease (PH-ILD; WHO Group 3) to improve the ability to exercise. Steve Van Wormer: Hi, welcome to I'm Aware That I'm Rare: the phaware podcast. I'm your host, Steve Van Wormer. Today we are here with Dr. Rodolfo Estrada from UT Health in San Antonio, Texas. He’s here to tell us about some exciting happenings that are taking place in the world of pulmonary hypertension and a new therapy that's been brought to market. Dr. Estrada, welcome. Rodolfo Estrada, MD: Thank you so much for having me. It's really great to be here. As you mentioned, I'm Rodolfo Estrada. I'm a pulmonologist at UT Health San Antonio, and there I lead the pulmonary hypertension program. My focus is now on caring for patients with pulmonary arterial hypertension or PAH and advancing research in this area. Steve Van Wormer: Dr. Estrada, it's a very interesting time in the world of pulmonary hypertension. There's a lot of moving parts, a lot of changes taking place in the community. I'd like you to share a little about where we are today. Rodolfo Estrada, MD: You're absolutely right. Even if we’ve made all this progress in PAH, PAH is still serious, and it's a progressive disease that can take a big toll, not only on the patients, but also on caregivers and families. We improved a lot in diagnosing it earlier and managing risk more precisely. We have more treatments available now more than ever, but we still are faced with big challenges. Diagnosis often comes up late, and many patients can’t tolerate the medication or don't have access to advanced therapies when they need them the most. For example, data from the REVEAL registry showed that only about a third of patients had received any form of prostacyclin, and half of those who died had never been started on IV therapy. And we get it. These medications really aren't easy. The side effects can be tough, and depending on how they're given, especially with IV or sub-Q options, there's a real risk of infection or complications from the delivery method. That's why inhaled prostacyclins have become an important alternative. Delivering the medications straight into the lungs helps reduce the side effects that you might get when the drug circulates around the body. But even with inhaled options, there are some hurdles, like needing frequent doses, challenges with breathing patterns, and a ceiling effect, at times, of how much you can increase the dose. Now here's where things get exciting. A new inhaled prostacyclin called YUTREPIA was recently approved. It's a dry powder inhaler that delivers medications using a special technology that’s called PRINT® that makes uniform particles just one micron in size. These particles travel deep into the lungs where they are needed the most. The medication comes in capsules you load into the device, and then you puncture the capsule and take two breaths four times a day. This device requires low effort from the patient, it seems to be well tolerated and easy to use, and hopefully this will help with the adherence of these patients. Steve Van Wormer: It's always an exciting time when there's a new tool in the toolbox for doctors and healthcare providers to offer patients. Can you tell us a little bit about your experience with this clinical trial and the patients that you saw that really led to this approval. Rodolfo Estrada, MD: Sure, happy to. In the Phase 1 study of YUTREPIA, they found that 79.5 micrograms of YUTREPIA gave similar systemic exposure to about nine breaths of nebulized treprostinil. Where in another analysis showed that patients had a greater survival and longer time before starting parenteral therapy when they were on doses greater than this threshold of 79.5 mcg four times a day. Then, there was a study called INSPIRE, which was a Phase 3 open-label, multicenter trial that included about 121 patients. These patients were either started on YUTREPIA or they transitioned from nebulized treprostinil. The main goal was to see if the medication was safe and tolerable, and it was. The study included patients with PAH and WHO Functional Class II and III. Everyone had to be able to walk at least 150 meters and have a good lung function. Most patients were on background therapies, and patients had been diagnosed with PAH for about seven years on average for those who transitioned, and about four years for the ones who were newly started. Those transitioning, had to be on stable nebulized treprostinil for at least three months. They also used an explanatory analysis to look at things like six-minute walk distance and patient-reported outcomes. On average, patients who were new to prostacyclin showed improvement, especially as doses increased, and those who transitioned didn't lose ground in their exercise capacity. Notably, a hundred percent of the patients who transitioned from nebulized treprostinil say they preferred to stay on YUTREPIA after a few months of trying it. Steve Van Wormer: Can you walk us through a little about how the medication was being used in the INSPIRE study or tell us what kind of doses was the study aiming to achieve? Rodolfo Estrada, MD: The way the trial was done is patients were started on 26.5 micrograms four times a day, with weekly increases up to a maximum of 212 micrograms four times a day. By two months, 78% of the transition group and 71% of the treatment-naive group were above the key threshold of 79.5 micrograms four times a day. At one year, 40% reached a dose equal or greater to 132.5 micrograms or what's the equivalent of about 15 breaths of nebulized treprostinil. In the open label extension, about one third of patients reached a dose equal or greater than 159 micrograms, which is about 18 breaths of nebulized treprostinil. Even at two years, there were patients who reached up to 238 micrograms, which is around 27 breaths of nebulized treprostinil. In our center, we had a couple of patients in the trial who reached some of the highest doses, even in a woman in her 70s, which again, trial patients may not necessarily represent the real world. They tolerated it well and stayed at low risk longer really without needing additional therapy. Steve Van Wormer: So in these trials, what were some of the potential side-effects that patients experienced as they went through the trial? Rodolfo Estrada, MD: That’s a good question. The side effects were similar to other inhaled prostacyclins like cough, throat irritation, headaches and dizziness. These were mostly mild to moderate and tended to show up more in the treatment-naive group, as you would expect. Importantly though, at one year, no patient in the transition group had to stop the medication because of cough, and only 2 patients in the treatment-naive group had to. About 10% left the study due to side effects, but none of them were serious adverse events that were linked to the medication. Steve Van Wormer: So you had this successful trial and that’s led to a successful approval. Now that there's a new drug in your toolbox, what happens when a new therapy comes into play into the real world versus when it’s used in a trial group of patients? Rodolfo Estrada, MD: When we're doing trials, we're trying to answer a very specific question. And to be able to answer that specific question, we try to narrow the population that we can get the answer for. What happens in real world is that then the exposure of whatever intervention we did, medication or whatever else we would do, would be then offered to a broader range of profiles. And then things that we may have not picked up on trials, then we pick it up in the real world, sometimes great, sometimes not as great. When you do a trial and it's a specific number of patients, usually a smaller number of patients than real world, as you get more exposure in the real world, we learn new things that we didn't know about it before. Steve Van Wormer: So what's great here in summary, doctor, is that we have a whole host of options for PAH patients, including YUTREPIA here, but also exciting for the PH-ILD population that has formerly only had one option. So, when a second option, a new option is laid out, how does that change the playing field for both of those subsets of patients? Rodolfo Estrada, MD: Yeah, it's a great point. We now have another inhaled option with YUTREPIA, which is now approved for not only PAH but also PH-ILD. It's a convenient dry powder inhaler that requires low effort from the patient, and it seems to be well tolerated and easy to use, which may help with the patient's adherence. From what we've seen, it offers a chance to deliver medication deep into the lungs, hit high doses, and potentially improve outcomes for patients who may not tolerate or access other forms of the medication. Steve Van Wormer: I really appreciate you being here today, doctor, to tell us about this exciting news for patients, exciting news for the healthcare providers like yourself, and thankfully to sponsors like Liquidia for the work they're doing to better the lives of patients with PAH and PH-ILD. Rodolfo Estrada, MD: Thank you for having me, Steve. It’s really been a pleasure talking to you about this today. And for the patients listening, while it is always exciting to have a new medication available in this space, it is very important that you discuss to the specific therapy plan that is best for your with your specific therapy providers and teams. My name is Rodolfo Estrada, and I'm aware that my patients are rare. Please see the Important Safety Information in the show notes. The Prescribing Information and Instructions for Use for YUTREPIA are available at Learn more about the Learn more about pulmonary hypertension trials at . Engage for a cure: #phaware Share your story: Like, Subscribe and Follow us: . #phawareMD #PHILD IMPORTANT SAFETY INFORMATION Before you take YUTREPIA, tell your healthcare provider about all of your medical conditions, including if you: Have low blood pressure Have or have had bleeding problems Have asthma or chronic obstructive pulmonary disease (COPD) Are pregnant or plan to become pregnant. It is not known if this product will harm your unborn baby Are breastfeeding or plan to breastfeed. It is not known if this product passes into your breast milk. Talk to your healthcare provider about the best way to feed your baby during treatment Tell your healthcare provider about all of the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements. YUTREPIA and other medicines may affect each other. Especially tell your healthcare provider if you take: Medicines used to treat high blood pressure or heart disease Medicines that decrease blood clotting (anticoagulants) Water pills (diuretics) Gemfibrozil (Lopid®) or rifampin (Rimactane®, Rifadin®, Rifamate®, Rifater®) What are the possible side effects of YUTREPIA? This product can cause serious side effects, including: Low blood pressure (symptomatic hypotension). If you have low blood pressure, this product may lower your blood pressure more. Bleeding problems. This product may increase the risk of bleeding, especially in people who take blood thinners (anticoagulants). The most common side effects of YUTREPIA are cough, headache, throat irritation and pain, nausea, reddening of the face and neck (flushing), fainting or loss of consciousness, dizziness, diarrhea, and shortness of breath. Like other inhaled prostaglandins, you may have trouble breathing after taking YUTREPIA because it may cause the muscles around your airway to tighten (bronchospasm). These are not all the possible side effects. Call your doctor for medical advice about side effects or if you have trouble breathing. You may report side effects to the FDA at or call 1–800-FDA-1088. The risk information provided here is not comprehensive. To learn more about YUTREPIA, talk with your healthcare provider. Please see and . For additional information, call 1–888–393–5732. /episode/index/show/phawarepodcast/id/36789935

Episode 523 - Rodolfo Estrada, MD 06/03/2025

Episode 523 - Rodolfo Estrada, MD Dr. Rodolfo Estrada, is a seasoned pulmonologists currently at UT Health San Antonio with significant experience in the management of patients with different forms of pulmonary hypertension. In this episode, Dr. Estrada will discuss the technology and clinical development behind YUTREPIA™ (treprostinil) inhalation powder and why it might be a good option for some PAH and PH-ILD patients. This Special Edition episode is sponsored by . Please see the Important Safety Information following this podcast. The Prescribing Information and Instructions for Use for YUTREPIA (treprostinil) inhalation powder are available at YUTREPIA is approved for the treatment of pulmonary arterial hypertension (PAH; WHO Group 1) and pulmonary hypertension associated with interstitial lung disease (PH-ILD; WHO Group 3) to improve the ability to exercise. Please see the Important Safety Information in the show notes. The Prescribing Information and Instructions for Use for YUTREPIA are available at Learn more about the Learn more about pulmonary hypertension trials at . Engage for a cure: #phaware Share your story: Like, Subscribe and Follow us: . #phawareMD #PHILD IMPORTANT SAFETY INFORMATION Before you take YUTREPIA, tell your healthcare provider about all of your medical conditions, including if you: Have low blood pressure Have or have had bleeding problems Have asthma or chronic obstructive pulmonary disease (COPD) Are pregnant or plan to become pregnant. It is not known if this product will harm your unborn baby Are breastfeeding or plan to breastfeed. It is not known if this product passes into your breast milk. Talk to your healthcare provider about the best way to feed your baby during treatment Tell your healthcare provider about all of the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements. YUTREPIA and other medicines may affect each other. Especially tell your healthcare provider if you take: Medicines used to treat high blood pressure or heart disease Medicines that decrease blood clotting (anticoagulants) Water pills (diuretics) Gemfibrozil (Lopid®) or rifampin (Rimactane®, Rifadin®, Rifamate®, Rifater®) What are the possible side effects of YUTREPIA? This product can cause serious side effects, including: Low blood pressure (symptomatic hypotension). If you have low blood pressure, this product may lower your blood pressure more. Bleeding problems. This product may increase the risk of bleeding, especially in people who take blood thinners (anticoagulants). The most common side effects of YUTREPIA are cough, headache, throat irritation and pain, nausea, reddening of the face and neck (flushing), fainting or loss of consciousness, dizziness, diarrhea, and shortness of breath. Like other inhaled prostaglandins, you may have trouble breathing after taking YUTREPIA because it may cause the muscles around your airway to tighten (bronchospasm). These are not all the possible side effects. Call your doctor for medical advice about side effects or if you have trouble breathing. You may report side effects to the FDA at or call 1–800-FDA-1088. The risk information provided here is not comprehensive. To learn more about YUTREPIA, talk with your healthcare provider. Please see and . For additional information, call 1–888–393–5732. /episode/index/show/phawarepodcast/id/36648690

Marc Simon, MD - phaware® interview 522 05/27/2025

Marc Simon, MD - phaware® interview 522 Decoding Pulmonary Hypertension: Echo and Cath Insights for Pulmonologists. Dr. Marc Simon shares his expertise on diagnosing pulmonary hypertension, emphasizing echocardiographic markers, right heart catheterization pitfalls, and risk stratification with the H2FPEF score. His insights help clinicians refine their diagnostic approach for better patient outcomes. This Special Edition episode is sponsored by . View PDF Slides . 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 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 . 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... /episode/index/show/phawarepodcast/id/36058850

Episode 522 - Marc Simon, MD 05/26/2025

Jean M. Elwing, MD - phaware® interview 521 05/20/2025

Jean M. Elwing, MD - phaware® interview 521 Dr. Jean Elwing, a leading expert in pulmonary hypertension, discusses groundbreaking advancements in treating pulmonary hypertension associated with interstitial lung disease (PH-ILD). For years, patients with this condition had limited treatment options beyond oxygen therapy and symptom management. However, recent studies have introduced new hope, showing improved patient outcomes and quality of life. Dr. Elwing emphasizes the importance of early diagnosis, ongoing research, and clinical trial participation in pushing the field forward. This Special Edition episode is sponsored by and . My name is Dr. Jean Elwing. I'm a Professor of Medicine and I'm the Director of the Pulmonary Hypertension Program at the University of Cincinnati. I've been there about two decades now, really focused the entire time on the care of patients with pulmonary hypertension and related illnesses. Over that time, we've built a large practice of pulmonary vascular disease related conditions and are trying to do our best to improve the lives of people we take care of. Today, I'd like to talk to you about interstitial lung disease and pulmonary hypertension. The type of pulmonary hypertension that develops in the setting of lung disease is called hypoxic pulmonary hypertension or Group 3 disease. This can happen in different types of lung diseases, including interstitial lung disease and COPD to name a few. But we're going to concentrate today on interstitial lung disease and its associated pulmonary hypertension. It's a very exciting time for patients with pulmonary hypertension associated with interstitial lung disease, because we now are making progress in this area. Five years ago, we knew that pulmonary hypertension was associated with this condition, but we didn't have a lot we could do to focus on the pulmonary hypertension except watching, giving oxygen, monitoring right heart failure symptoms and treating them and referral to transplant in appropriate patients. But recently, there's been more of an interest in assessing medications for the treatment of the pulmonary hypertension that occurs in the setting of interstitial lung disease. We've learned over time that this is not easy to treat. We've tried multiple medications without successful outcomes. In small studies, case series, but more recently we studied inhaled treprostinil for the treatment of interstitial lung disease and pulmonary hypertension and found that this was an intervention, a therapy that could improve outcomes. So for the first time, we have hope that we can change the outcome in this disease, slow it down, pump the brakes, give patients a little more time, and hopefully feel better, do more during that time. We would love to have a cure for it. We would love to be able to say we are turning the dial back to zero. We're not there yet, but there's a lot of interest now. There's new studies coming, new therapies being looked at. I have a lot of hope that we're going to be able to make progress here. Interstitial lung disease is a condition where you have inflammation and scarring in the lungs. It can happen from multiple different reasons. It could be related to exposure, it could be related to underlying autoimmune disease or multiple other factors can contribute. But at some point in patients' lives, they may develop a new problem associated with that, and that's pulmonary vascular disease and pulmonary hypertension. At one point, we really thought that that only happened when the disease was quite advanced, but we've learned over time, it can happen at any time in the course of a patient with interstitial lung disease. Once it develops, it's associated with a lot of different things, including more oxygen requirement, less exercise tolerance, more exacerbations, and a shorter life expectancy. It is a trigger for us to think about, “Hey, what can we do to try to slow this down?” We try to optimize the interstitial lung disease, manage everything that's contributing, take away any potential triggers for worsening, manage infections quickly, so that doesn't cause a worsening event requiring hospitalization and additional intervention. But the pulmonary hypertension piece is the part that, as I mentioned, did not have an intervention previously. Now, when we see patients that have signs that their pulmonary vascular disease may be progressing, like more oxygen, lower exercise tolerance, more fatigue, right heart failure symptoms, we look, we obsess with an echocardiogram. We proceed to right heart catheterization to evaluate for the possibility of true elevated pulmonary pressures or pulmonary hypertension. Then, we offer treatment to the appropriate patients. That treatment's not easy, it's an inhaler, four times a day, but as I mentioned, we've learned that it can be very helpful to patients based on the INCREASE trial, where we saw that patients were able to ambulate further. It reduced stress on the heart based on a lab marker called BNP, and it reduced worsening. So this is just the tip of the iceberg. We're just starting this journey with pulmonary hypertension in the setting of interstitial lung disease, but at least now we have a starting point. As I mentioned, there is a therapy available and approved for patients with interstitial lung disease and pulmonary hypertension, and we're working on others through research. What I have to remind everyone is to say thank you to all those individuals who participate in . They give us options. Without their efforts and all the work they do to participate in trials, we wouldn't have new medications. So I just encourage you, if you are the right person that meets criteria for a to consider it. Look at the options. See if that might be something you would like to explore. Not only could it be something that would benefit you, potentially, it also has the opportunity to impact many other individuals affected by this condition. Pulmonary hypertension has so many faces, and for so long we've really concentrated on pulmonary arterial hypertension Group 1 disease. But now, I'm so happy to say that we are getting options for therapies that are impacting outcomes in many groups of pulmonary hypertension, including patients with lung disease. We have a long way to go. We've only touched the tip of the iceberg on this. ILD individuals have an option for treatment. We have many other conditions that of course, over time we hope to better understand and hopefully with that understanding be able to impact the development of pulmonary hypertension and control of the condition to allow patients to have longer, fuller, and more active lives. Thank you so much for listening. My name is Dr. Jean Elwing, and I'm aware that my patients are rare. Learn more about pulmonary hypertension trials at . Engage for a cure: #phaware Share your story: Like, Subscribe and Follow us: . #phawareMD #PHILD #PHOCUSstudy #PROSERAstudy /episode/index/show/phawarepodcast/id/35841670

Episode 521 - Jean M. Elwing, MD 05/19/2025

Seth Hall, MBA, RRT - phaware® interview 520 05/13/2025

Seth Hall, MBA, RRT - phaware® interview 520 Seth Hall, MBA, RRT, takes listeners on a journey through the past, present, and future of inhaled therapies. Discover how these treatments have evolved, the life-changing benefits they offer, and the revolutionary technologies that could redefine outcomes for PAH and PH-ILD patients. This Special Edition episode is sponsored by . My name is Seth Hall. I started my career as a critical care respiratory therapist in Washington D.C. Over the years, I traveled around the country working at various academic centers; Duke and Stanford and Columbia, and several others. I was just like a sponge. That experience just allowed me to keep learning, growing, and luckily, I was able to surround myself with some really great mentors. I landed in respiratory and took care of a lot of patients with pulmonary hypertension in my past, throughout my years working clinically. I'm actually from a very small coal mining community in West Virginia. Some of my current research I do independently from work also revolves around addressing barriers and access to care with patients with cardiopulmonary illnesses, specifically in rural communities. I'm very passionate about advocating for patients with cardiopulmonary diseases and illnesses, and very lucky and fortunate to have been involved in the care of PH patients in my past. Currently I work as a medical science liaison or MSL at , and we strive to bridge the gap between that clinical research and finding solutions to unmet needs for patients. We really help bridge that gap of clinical research and the scientific discussion and exchange. With my respiratory background, something I've always been interested in is just the evolution of inhaled therapies and how we've got to where we are now with managing some of these complex respiratory diseases. Last year, we published a piece in Respiratory Therapy: A Journal of Pulmonary Technique where we talked about just that. We looked at the historicity benefits, future potential options for inhaled therapies, and we really focused on emerging technologies. We wanted to really focus on how targeted drug delivery could potentially transform care for millions of patients. Looking back, it actually goes back pretty far. Almost 4,000 years, actually. Some early medical practices that emerged in India over 2000 BC, where they looked at inhaled therapies for opening up the lungs and what we refer to as bronchodilatory properties. Then, around 1500 BCE, Egyptians were looking at inhaling vapors and other plant medicinal purposes for other respiratory relief. Even when you look back at ancient Greeks under Hippocrates, they developed one of the earliest actually medical devices, and that was simply just a pot with a reed and you inhaled medicines. These vapors were therapies for patients. Then, these practices, which we see all over the world, were found in Central and South America and Africa. They were the early foundation for what we're doing today in the development of modern inhalation therapy. This evolution of inhaled therapies, it really just reflects the ongoing innovation to provide more solutions for people around us. To fast-forward, we now have nebulizers. These emerged around the 19th century. These delivered medicine via an aerosol. Think of a liquid droplet. It can be very effective, but sometimes can be quite cumbersome, with parts and pieces due to the size and assembly. You can imagine being a patient and trying to travel with this. If you have an active lifestyle, it might not be practical for daily use. Then, fast-forward a little bit more looking into around the 1950s, metered-dose inhalers came around or MDIs. These were a good alternative to nebulizers, however, they really require precise coordination. What I mean by that is essentially the patients have to actuate the drug and then time it with their inhalation or with breathing in. You can imagine how for some patients this could be a challenge. Now we have dry powder inhalers or DPIs, which emerged around the 1990s, that really addressed some of those limitations that we spoke to with earlier devices. They're simple to use, they're portable, but they're actually breath-actuated. In order to disperse the medication and get them where they needed to go, the patient just takes in a deep breath. This really helped out with usability and patients adhering to medicine, because we know if we make it easier for patients to take their medicine, they're more likely to be compliant with their treatments. Direct lung delivery has proven itself to be the cornerstone for effective treatment, especially for respiratory diseases. By giving the medication directly to the lungs, we are bypassing potential systemic side effects. The intended site of action is in the lungs, that's where we're delivering the medicine. Whereas, if you're getting medicine via orally or IV administration, you're now exposing other parts of the body to that medication, as well. Essentially, the localized drug delivery can help enable lower therapeutic dosing. You can use less drug. It provides a very rapid onset, you're going to where the drug needs to be. This targeted delivery for symptoms and all different types of diseases, you might have bronchoconstriction or vasoconstriction, inflammation. Essentially, you're just targeting exactly where the drug needs to go. DPIs have become a preferred choice for many respiratory diseases due to their portability, their ease of use, patient adherence, making it easier for patients to take their medicine. Unlike the metered-dose inhalers or the MDIs we just talked about, DPIs don't require that precise timing. They don't have a propellant. They don't require a spacer to take the medication. Then, their compact design makes it ideal for active patients on the go that are out and about with their families. From a functional perspective, DPIs are breath-actuated. What that means is essentially it utilizes the energy of their own breath or their inhalation to overcome these cohesive forces that are holding the powder together. That helps to break up the particles. That process of breaking up the particles is referred to as de-agglomeration. So, the way that devices are engineered with DPIs, there's an internal resistance, and this resistance within the device provides a mechanical assistance with that de-agglomeration, and that helps with the distribution of the drug particles to the lungs. Despite these advancements that we've had in respiratory treatments, inhaled drug deliveries still remains pretty poor. For instance, in the case of DPIs, what's currently available, patients with restrictive lung diseases might have a limited ability to use some of these higher resistance inhalers that the inhaler needs to break apart the medication. This essentially inhibits the complete particle de-agglomeration for the patients. Then, we know that when there's inadequate de-agglomeration that the dry powders are going to have more variability in their particle sizes. Some of these larger particle sizes tend to deposit more in the upper airway, which we refer to as the oropharynx, which can lead to patients having to cough. Apart from increasing the potential upper airway irritation and the cough, you also have insufficient delivery of medication now to the lower airway where you want the drug to be. This could potentially result in increased systemic absorption and creating additional tolerability issues and challenges for patients trying to take their medicine. So, a critical advancement would be if in the inhalation delivery space, we could make these particles uniform in their physical and chemical flow properties that might help resist this clumping together. Some of these advancements would really enable the use of lower resistance inhalers, because it wouldn't necessitate that you need to de-agglomerate with a high resistance. That means less effort that the patient requires for them to take their medication. One novel formulation approach that has the potential to significantly advance the manufacturing of DPIs is something referred to as by Liquidia. PRINT®, which stands for particle replication and non-wetting templates, it actually originated in the electronics industry with microprocessors. Clinically, it's been studied though in vaccines and antivirals, ophthalmology, and even in topicals. Currently, it's of high interest in the inhaled therapy space. PRINT® Technology offers the unique ability to control for inhaled particle size and shape, giving a higher degree of confidence that the drug is reaching the targeted lung region where it needs to go. It's essentially a mold technology. Think of ice cubes in an ice tray. They all look the same shape and size. That's what PRINT® does but on a micro level, with the actual formulation of these DPIs. The geometric precision and shape of these particles can potentially significantly enhance the aerosolization and potentially allowing these PRINT® formulations to be compatible with a diverse array of DPI devices, whether you have low or high resistance. Now, you can tailor the medicine specifically to the pathophysiology of whatever respiratory condition you're trying to treat. PRINT® Technology is designed to ensure that you have the homogeneity of the particle, concentration, and it's a critical factor in maintaining consistent dosing. We know that consistent dosing leads to therapeutic efficacy. This uniformity, it potentially mitigates the variability in drug delivery for patients. As a respiratory therapist, I'm actually really excited. I think the evolution of device technology, along with advancements in drug formulations, holds great promise in improving pulmonary drug delivery. I mentioned formulation, so I'll just grow on that a little bit too. We have emerging liposomal formulations that are being studied right now in clinical trials that might also mark a significant milestone in this ongoing effort. Liposomes are essentially nanoscale lipid vesicles that surround the medication or what we refer to as encapsulate. That's to help extend the release profile of the drug. It also can help enhance the stability, and now, you have a reduction in the dosing frequency required by the patient. These innovations could potentially provide sustained therapeutic benefits for a wide variety of respiratory illnesses, reducing the burden of the frequent dosing for the patients, and potentially improving patient adherence by making it easier on them. All in all, the development of inhaled therapies really demonstrates our relentless pursuit, striving for more tolerable, patient-friendly just more options in the treatment of many conditions in the respiratory space. Innovations such as PRINT® Technology and liposomal formulation really underscores the commitment to optimizing drug delivery for some of these really challenging conditions. As research continues and we have more data, the future of inhaled therapies holds immense potential to really address some of these unmet needs, and most importantly, improve the quality of life for patients all over the world. My name is Seth Hall, and I'm aware that the patients we serve are rare. Learn more about pulmonary hypertension trials at . Engage for a cure: #phaware Share your story: Like, Subscribe and Follow us: . #phawareMD #PHILD #PRINTTechnology /episode/index/show/phawarepodcast/id/36058550

Episode 520 - Seth Hall, MBA, RRT 05/12/2025

Richard Channick - phaware® interview 519 05/06/2025

Richard Channick - phaware® interview 519 Dr. Richard Channick, dives into the evolving world within pulmonary hypertension -- interstitial lung disease (PH-ILD). He sheds light on why early diagnosis matters and how new therapies are transforming care. Learn about the latest FDA-approved treatment and what’s on the horizon. This Special Edition episode is sponsored by and . Hello, I'm Rich Channick. I'm Professor of medicine at UCLA Medical Center and Co-Director of the Pulmonary Vascular Disease Program at UCLA. I've been there for the last six-and-a-half years, but have been involved with pulmonary hypertension for over 30 years from my fellowship in the '80s onwards. So, I've gotten to see all the evolution and changes that have occurred in this exciting field.Today, I would like to talk about, really, an exciting, evolving area within pulmonary hypertension, which is pulmonary hypertension in the setting of interstitial lung disease or ILD, as we call it. The reason why this is exciting is that there actually are now emerging therapies for pulmonary hypertension due to ILD. The other important point to note is that this is actually more common than a lot of other forms of pulmonary hypertension. So, what are we talking about here? What's the terminology? Well, ILD means interstitial lung disease, and very simply, it's scarring or fibrosis within the lungs. When we talk to our patients who have pulmonary arterial hypertension, we often say, "Your lungs are fine. It's the blood vessels running through your lungs where the problem is." Well, in ILD-PH, that's not the case. In ILD-PH, the lungs are not normal. There are a number of things that can cause this fibrosis or scarring of the lungs.It can be due to some exposure. It can be due to another disease, like an autoimmune or connective tissue disease. It can be due to what we call idiopathic, or we don't know the cause for the pulmonary fibrosis. So, there's a lot of different causes. But what we do know is that in some patients, and maybe as many as 30% of patients, pulmonary hypertension or high blood-pressured lungs will develop as a result of the fibrosis.Again, that distinguishes it from other forms of pulmonary hypertension, like PAH, where the lungs may be fine, or left-sided heart disease or pulmonary emboli. This is a distinct subgroup within pulmonary hypertension, also referred to as group three. So, that's how we define the problem. What about treatment? This is, again, where the excitement is. Because there's now one FDA-approved therapy for ILD-PH, and then there are a number of others being looked at. There are some treatments for the ILD itself that are approved. Those treatments have variable effect, and there are some side effect issues.We know that if the pulmonary hypertension develops with ILD, that needs to be treated, because the prognosis in patients who have ILD-PH is worse than if they didn't have PH. The ability to treat the PH in ILD, and to show a benefit will help patients, certainly from a point of view of quality of life and their exercise capacity, hopefully will improve outcomes.Right now, in patients with ILD and ILD-PH, if it's severe enough, lung transplantation has historically been the only option, and that has its own problem. So, if one can find a treatment that can prevent or at least delay the need for lung transplantation, that's a big victory.In addition to the FDA-approved therapy, which is inhaled treprostinil, it's a long-acting prostacyclin-type drug that's also used in PAH. But the inhaled form was shown to be beneficial in ILD-PH, and therefore it was FDA-approved for that. In addition, there are a number of other drugs that are going through the development, mainly in ; similarly to inhaled treprostinil, looking at the ability of these drugs to improve exercise capacity, improve the hemodynamics, and hopefully improve the outcomes.The interest in ILD-PH has actually always been there, but it's always been a little bit of a head-scratcher. Because early on, there were some studies showing that some of the drugs we thought were exciting in PAH didn't necessarily help patients with ILD-PH. A couple examples actually were harmful. So, I think that slowed things down a little bit.But in recent years, again, with some of these newer therapies, and maybe it has to do with the availability of inhaled therapies, because when you have a lung problem, like ILD, PH is an attraction to inhaling the treatment where it gets right to the lungs, and may not have effects outside the lungs. So that, I think, raised the interest even more.Again, with inhaled treprostinil showing a benefit, a lot of the other newer agents, or that have new molecules, became aware really that this is a big need for which there's not a lot of effective treatments. I guess that's a little in contrast, of course, to group one or PAH, where we now have essentially 15 approved therapies. So, certainly, again, I'm a physician, I'm not a business person. But from a strategic business point of view, looking at an area where there's only one approved treatment versus 15, you could see where that might lead.The question is, how big is the pot? The pot may be bigger than we think of these ILD-PH patients, because one of the challenges is the recognition that a patient may be diagnosed with ILD or lung disease by an ILD specialist, but nobody's thinking about pulmonary hypertension. We believe, and we have some data to suggest, that may be underdiagnosed. So, the pot may actually be quite large of patients with ILD and pulmonary hypertension.I think it's very important that patients obviously are their own advocates in everything, but certainly in this area. If a patient has interstitial lung disease or pulmonary fibrosis and is being managed by even a specialist in that, to at least raise the possibility that, could they also have pulmonary hypertension? And let their healthcare provider know that they're concerned about that.Certainly, in the setting where, let's say, somebody's getting worse, so your symptoms are worsening, you're getting a little more short of breath, but the doctors are saying, "Well, your lungs are stable," the way we follow interstitial lung disease is a little different. We're getting pulmonary function tests, we may be getting imaging or CT scans of the chest. That may show stability of the lung disease, but yet the patient is feeling worse. That could be a sign or clue that pulmonary hypertension is developing.Thank you very much for listening. My name is Dr. Richard Channick, and I'm aware that my patients are rare. Learn more about pulmonary hypertension trials at . Engage for a cure: #phaware Share your story: Like, Subscribe and Follow us: . #phawareMD #PHILD #PHOCUSstudy #PROSERAstudy /episode/index/show/phawarepodcast/id/35841445

Episode 519 - Richard Channick, MD 05/05/2025

Ioana Preston, MD - phaware® interview 518 04/29/2025

Ioana Preston, MD - phaware® interview 518 Dr. Ioana Preston explores the emerging field of pulmonary hypertension associated with interstitial lung disease (PH-ILD). She discusses the growing recognition of PH-ILD, especially after the introduction of inhaled treprostinil as a treatment, and highlights the importance of early screening and diagnosis. Dr. Preston also delves into the challenges of treating rare diseases, the evolution of research, and the hope for future therapies that could significantly improve patients' lives. This insightful conversation sheds light on a critical yet often overlooked aspect of pulmonary care, urging clinicians to stay vigilant and informed about PH-ILD's complexities. This Special Edition episode is sponsored by . I'm Ioana Preston. I'm a physician and the pulmonary hypertension expert. I'm the Pulmonary Hypertension Director at Lahey Hospital and Medical Center in Burlington, Massachusetts. Today, I would like to talk to you about a rare form of pulmonary hypertension -- pulmonary hypertension associated with interstitial lung disease or ILD. PH-ILD is typically a disease of an adult. There is a small population of children, but it’s kind of a different entity. It's typically an adult disease because mostly adults develop interstitial lung disease. If we look at PAH Group 1, there are more women than men with a Group 1 PAH. This ratio does not translate in PH-ILD, where the population is more mixed. A typical PH-ILD patient is adult or elderly. They could be men or women. It's much broader in presentation. It's not a very specific population that we need to look at. That's very important, because we have to keep our mind open to screen all patients who have ILD for pulmonary hypertension. Now, at the 7th World Symposium on Pulmonary Hypertension that just took place in summer of 2024 renamed this entity and called it ILD-PH. So, interstitial lung disease with PH associated. Now, we haven't talked about this entity for a long time until recently. Why haven't we talked about it? Because there were no therapies available. We were not looking for pulmonary hypertension development in patients with ILD such as pulmonary fibrosis. It was kind of in the back of our minds as clinicians. But because there were no therapies available, we couldn't have any impact on the well-being of our patients with ILD who may develop pulmonary hypertension. Now, recently, after many, many years and many, many trials that failed, couple of years ago, a Phase 3 clinical trial showed that inhaled treprostinil is efficacious in treating pulmonary hypertension associated with interstitial lung disease. At that point, the door was opened and we clinicians understood that we need to look for this development in patients with ILD. We need to recognize it early. We need to screen for the presence of pulmonary hypertension in ILD. We need to treat it if it is available. Moreover, I think what is also important is to help the community develop other therapies for PH-ILD, because the story just begins. It doesn't end here. So, developing other therapies by enrolling patients with PH-ILD in clinical trials, I think it's a very important aspect that we need to focus on in the next years. So, going back to PH-ILD, what it means is the development of high blood pressure in the lungs or pulmonary hypertension in patients who have underlying forms of, or different types of pulmonary fibrosis. Clinicians now need to focus and learn how to screen and identify this entity. This educational program that occurred at CHEST 2024 is focused on teaching physicians and clinicians and healthcare providers how often and what tests are required to look for pulmonary hypertension, how to diagnose it, how to understand the severity of the pulmonary hypertension and how to treat it. So, now we have a better understanding and a more clear plan of how to approach pulmonary hypertension in the setting of interstitial lung disease. Going back 30 years ago, when I was a young physician in training, at that time, we had only one treatment for pulmonary arterial hypertension, which is Group 1 PAH. We had only Flolan. At that time, what was happening is we would diagnose patients with PAH and then we would wait for the disease to become severe, and then we would start therapy, because it was an infusion therapy. But this first drug that was developed in PAH opened a huge opportunity in research and clinical practice in PAH. Now, we have 14 therapies. Now, fast-forward in the 2020s, the same is happening. The same story is being repeated with PH-ILD. Up until very recently, all the clinical trials have failed, so we had no therapy for PH-ILD. Now, we have one therapy, so the door has opened. I am very hopeful that we will have more and more therapies in the future, in the next years to come to offer our patients to better control their disease, to improve their symptoms, and hopefully to have an impact on their life. That's why I'm really hopeful that we will have more options for our patients in the future. So, now fast-forward medical history to the 2020s, for PH-ILD there is a wealth of clinical research in clinical trials that are looking at different drugs and compounds to add on to the current therapies that we have available. There's very interesting research. I'm very hopeful that in the very near future, we will have more opportunities to treat PH-ILD effectively and improve the breathing, the activity, and the lifestyle of patients with PH-ILD. The rare diseases are challenging in and out of itself. The more rare the disease, the less experience the clinician has. We are humans and we think of more common things more often as a cause of our patient's symptoms. We forget the rare conditions, lack of experience, the fact that we in general clinical practice, not in my clinic, but in general clinical practice, you don't tend to see many patients with pulmonary fibrosis or ILD. Therefore, it's difficult to remember the subsets of comorbidities or other conditions that an ILD patient can develop. I think the first step is the fact that there's a rare disease, it's way in the back of the clinician’s mind. That's why it's very important to increase awareness of rare diseases such as PH-ILD. It's very important to remind clinicians to not forget about this entity and also to provide patients with pulmonary fibrosis information about this possible occurrence during their lifetime. But I have to say, if you look at different reports, I remember one report from Virginia from Inova Fairfax. It’s a large lung transplant center, and there patients with ILD get lung transplants. So, there is a strict requirement to look for pulmonary hypertension at the beginning of lung transplant evaluation, and also to evaluate for pulmonary hypertension just before they have the transplant. This report showed that at the time of transplant, 84% of patients with ILD just before they go to the OR, have pulmonary hypertension. So, we are talking about pulmonary fibrosis and all sorts of interstitial lung diseases. They're not common, they're rare. However, as the disease progresses, the vast majority of these patients will develop pulmonary hypertension. So, we really have to be cognizant of this important occurrence. My name is Dr. Ioana Preston, and I'm aware that my patients are rare. Learn more about pulmonary hypertension trials at . Engage for a cure: #phaware Share your story: Like, Subscribe and Follow us: . #phawareMD #PHILD /episode/index/show/phawarepodcast/id/35535560

Episode 518 - Ioana Preston, MD 04/28/2025

Raj Parikh, MD, MPH - phaware® interview 517 04/22/2025

Raj Parikh, MD, MPH - phaware® interview 517 Dr. Raj Parikh from Hartford Hospital discusses the development of the PH-ILD Detection tool, a screening tool designed to help detect pulmonary hypertension (PH) in patients with interstitial lung disease (ILD) at an early stage. Early detection is critical, as there is often a significant delay in diagnosis of PH in ILD patients, leading to worsened outcomes. This Special Edition episode is sponsored by . My name is Raj Parikh. I'm the Director of the Pulmonary Hypertension Center at Hartford Hospital in Hartford, Connecticut. I did a lot of my training kind of all over. I went to medical school in New Orleans, Chicago, ended up in Boston, and then made my way back home to Connecticut where I grew up. I've been at Hartford Hospital for the last four years. I started the Hartford Hospital's Pulmonary Hypertension Program from scratch, and I've been building it up since then. I got involved in Pulmonary Hypertension really during my fellowship at Boston. I really wanted to get involved in the rare disease space of PH, where patients are far and few between, but the ones that are there, they have pretty significant morbidity, mortality, and a poor prognosis. There's limited treatment options and there's limited specialty care for these patients. I really wanted to come back home to my state of Connecticut and build up a program in sort of the area that I grew up in. Today, I want to talk to you about the PH‐ILD Detection tool that Hap Farber, MD and I have been working on for a couple years. Now, it's in the community. We're encouraging all interstitial lung disease, ILD specialists, general pulmonary docs who see ILD patients to really use this as a way to work on early detection of pulmonary hypertension in interstitial lung disease patients. The reason behind developing the PH‐ILD Detection tool was to really focus on early detection and early screening for pulmonary hypertension that's associated with ILD. The impetus behind that was the development of the first and only FDA approved therapy for PH-ILD, which is inhaled Treprostinil. That was FDA approved back in 2021 after the INCREASE clinical trial. The PH-ILD Detection tool, the real spirit behind it is patients with interstitial lung disease that develop pulmonary hypertension carry extremely poor prognosis. They need more oxygen. Their quality of life is worse. Their longevity of life and their mortality is worse, as well. These are things we know. We've studied the PH-ILD population for years and years. This is well-established stuff. The key now that we have a therapy that can A, improve the patient's walk distance and therefore their quality of life. B, keep them from having any sort of clinical worsening like ending up in the hospital or having more right heart failure. These are all findings based on the INCREASE trial. So the key really is to detect the pulmonary hypertension as soon as possible in ILD, not just screen for it once a year, or test for it when you meet the patient for the first time and then test for it again every five years. This is not like colon cancer screening or lung cancer screening. This is active assessment every time you see an ILD patient, you should be thinking, “Okay, do they now have signs of pulmonary hypertension? Should I now be concerned about pulmonary hypertension or should I not be?" There is no standard protocol or standard practice when it comes to screening and detecting for pulmonary hypertension in ILD patients. Back in 2022, Hap and I really developed eight parameters for PH-ILD detection. We base these parameters off of things that you should routinely already be using to assess a patient's interstitial lung disease. We're talking about 6 minute walk tests, physical exam, pulmonary function testing, assessing whether the ILD patient needs oxygen or not, blood tests, CAT scans, and their prior history and comorbidities. If we take these eight parameters and we assess, okay, which parameters have a higher weight compared to lower parameters that have maybe not as much of a weight in terms of predicting for pulmonary hypertension? We took these eight parameters and basically created a 12 score tool. The score can be anywhere from zero to 12. Four parameters have a weighted score of two points. Four parameters have a weighted score of one point, therefore equaling a max score of 12 points. Basically, depending on what you score from zero to 12, you are stratified into either low risk for pulmonary hypertension ILD, intermediate risk for PH-ILD, or high risk for PH-ILD. A score of three or below is low risk. A score of four to five is an intermediate risk. A score of six or higher is actually high risk for PH-ILD. What does that mean? What does it mean if you're low versus intermediate or high? Well, that should really dictate what are your next steps. If you're low risk, you should reassess the patient at your follow-up visit, whether that's at three months or six months or whatever. If you're intermediate risk, you should get a screening echocardiogram for that patient to make sure there's no signs or development of pulmonary hypertension or right ventricular disease on that echo. If you're high risk, that's a score of six or higher on the PH-ILD Detection tool, you should not only order an echocardiogram, but you should be calling your nearby your local pulmonary hypertension specialist or pulmonary hypertension center and say, "I have a patient with interstitial lung disease. I have a high suspicion for pulmonary hypertension, can you get them into your clinic? Can you get them in for a right heart catheterization for a definitive diagnosis?" When we developed this score, we not only first developed it internally retrospectively, but once it was initially published, we discussed it and presented it at an oral presentation at CHEST back in Nashville, so that was a couple of years back. We then actually had seven centers used the score prospectively, and we validated the score by doing a multi-center validation cohort study. That study actually upheld a very significant area under the curve, very significant sensitivity and specificity for a score of six or higher to really strongly predict pulmonary hypertension in interstitial lung disease patients. As a result of this, we've been working on promoting the use of this PH-ILD Detection tool with local ILD specialists, local general pulmonologists. We use this score not only to predict or increase suspicion for pulmonary hypertension, we've done some other data and we actually presented this information at CHEST, this past year at Boston, where the higher the score you have, the worse your right heart cath hemodynamics are, and therefore the worse your prognosis may be. Some of that is almost common sense, but it's nice to kind of see pen to paper and see that correlation, as well. We've actually been working on seeing if we can create an app for this score. Now, Hap and I are creating an abbreviated version of the PH-ILD Detection tool to take it instead of eight parameters with 12 points, can we make it three parameters? Can we simplify it even further and make it as simple as possible so that the community pulmonary doctor, the community ILD specialist -- all of them can really focus on how simple it can be to detect and screen for pulmonary hypertension. Mostly because we know that once patients develop PH with ILD, the prognosis is so poor that we want to really act fast. We want to get them diagnosed soon. If we can diagnose them quickly, we can treat them with inhaled Treprostinil. We can mirror some of those outcomes that we saw with the INCREASE clinical trial, and get these patients having a better quality of life, better walk distance, lower proBNP scores, keep them out of the hospital, so on and so forth. We know from PAH pulmonary arterial hypertension and the REVEAL registry, there's almost a three year delay in diagnosis from the time a patient develops cardiopulmonary symptoms to the point B, which is when they actually have a formal PAH diagnosis. Three years. Those three years are met with seeing different specialists, being in and out of the hospital, having a worsening quality of life because they’re always short of breath and overall just poor more prognosis. If we take that, do we have that exact number when it comes to PH-ILD? No, but we do have an extremely wide range of epidemiology when it comes to PH existence with ILD. PH can range anywhere from 12% to 86% in ILD patients. Why do you have such a wide range? That's because we don't know when to look. We don't know how to look. A lot of times we don't even look and we're getting a lot of that data that 86% is sometimes showing up on autopsy results and transplanted patients. Then, we're looking back at those autopsy or transplanted lungs and saying, "Oh wow, those patients not only had ILD, they actually had PH as well." That's not something to necessarily be proud or happy about. So it kind of is in the same boat as, what is our delay in diagnosis? What is the window of opportunity that we need to really diagnose and intervene so we can make a difference? There will be a point of no return when it comes to ILD patients with PH. The same way there is sometimes a point of no return with PAH where the patients get so advanced that they're meeting them in the intensive care unit and they're meeting them really on what we call rocket fuel. These patients are looking for the Hail Mary to get better. You're not meeting them in the office, you're not trying to do a 6 minute walk test on them these patients can't even do a 6 minute walk test when they're sometimes at that point of no return. So really what is the sweet spot? I think it is trying to mirror what we went through with PAH several years ago. Developing a registry, understanding more of the referral patterns for PAH and we're trying to extrapolate all of that information and bring it now into this PH-ILD space, as well. I know I'm speaking to a lot of the providers and doctors who are involved with taking care of ILD patients, but really switching gears and thinking about it from the patient perspective. If you're a patient who has been diagnosed with any of the many subtypes of interstitial lung disease, I think it's important to be aware of this concomitant process that can occur and that can develop, which is pulmonary hypertension. It is difficult to tease out when you have worsening cardiopulmonary symptoms, worsening breathing symptoms. Is that the interstitial lung disease? Or is that something new such as pulmonary hypertension? I think it's important to think about that and be open with your provider, with your specialist, with your pulmonologist and say, "I'm now feeling this way, and I'm now using this much more oxygen, and wasn't my 6 minute walk distance this far last time and now it's down to this time? Could this be something else? Is this just not necessarily worsening interstitial lung disease or is this a second process?" A second process that now we know we can treat and we can make better. I think that's important to sort of think about. You can be your best advocate when it comes to going into your provider's office and really telling them exactly how you're feeling, and what you're feeling, and how it's different from prior. My name is Dr. Raj Parikh, and I'm aware that my patients are rare. Learn more about pulmonary hypertension trials at . Engage for a cure: #phaware Share your story: Like, Subscribe and Follow us: . #phawareMD #PHILD /episode/index/show/phawarepodcast/id/35840550

Episode 517 - Raj Parikh, MD, MPH 04/21/2025

Ron Zolty, MD - phaware® interview 516 04/15/2025

Ron Zolty, MD - phaware® interview 516 Dr. Ron Zolty delves into groundbreaking advancements in treating pulmonary arterial hypertension. From the historical use of vasodilators to the revolutionary promise of sotatercept and seralutinib, Dr. Zolty unpacks how science is moving closer to halting—and possibly even reversing—PAH. This Special Edition episode is sponsored by . My name is Ron Zolty. I'm a cardiologist working in advanced heart failure and heart transplantation. In my training, I had to do a lot of catheterizations in patients with pulmonary arterial hypertension. I trained at the University of Colorado in Denver, which is considered one of the best centers in pulmonary arterial hypertension. Working with patients in the cath lab, I fell in love with PAH, now leading a pulmonary hypertension program here in Omaha, Nebraska. Today, I would like to speak about some innovations in the field of pulmonary hypertension. As you may know, pulmonary arterial hypertension is a progressive, lethal disease. Patients, unfortunately, die from pulmonary hypertension if not treated. We should go back a little bit to the pathogenesis at the mechanism of what we believe causes pulmonary arterial hypertension. We know that when patients suffer from pulmonary arterial hypertension, they have what we call endothelial disruption. Endothelial is the inner layer covering the vessel of any vessel and especially the pulmonary arterial tree. If you have any damage of this endothelial layer, you are going to make some small thrombi, some small clots. One of the initial treatments of pulmonary hypertension was in the eighties to treat these patients with anticoagulation. Unfortunately, there was never any prospective study looking at the benefit of anticoagulation, only retrospective studies. Most of them showed that there is some benefit of anticoagulation blood thinner. However, because there was never any prospective study, it's just a 2b indication, not everyone needs to be on anticoagulation because again, it hasn't been shown really to improve survival in patients with PAH. The second main phenomenon that patients have with pulmonary hypertension is vasoconstriction. Vasoconstriction, meaning that the vessels tighten when you do have the disease. That's the reason for the three classic pathways we treat today. Pulmonary arterial hypertension, we know that patients with PAH have too much endothelin, which is one of the most potent vasoconstrictors we have in our body. So we block this endothelin causing less vasoconstriction and vasodilator effect. We also know that patients with PAH don't have enough prostacyclin, so we do substitute this lack of prostacyclin with some prostacyclin. We do have IV, inhaled, and oral prostacyclin to give to patients. The third pathway, which is also a vasodilator pathway, is the lack of nitric oxide. Patients with pulmonary hypertension have a lack of nitric oxide, and therefore we give them a PDE5 inhibitor like sildenafil or tadalafil or a SGC stimulator like riociguat to increase the nitric oxide pathway, increasing cyclic GMP. Cyclic GMP, really vasodilates. But all these therapies, these classic therapies do not stop the progression of the disease. They slow down the progression of the disease without stopping the disease. We also know, and that's the last point and the newest point I want to make, when patients do have pulmonary arterial hypertension, the wall of the vessel gets thicker. If the wall gets thicker, the lumen where the blood travels gets smaller and smaller. That's the reason why patients get less blood, less oxygen, less hemoglobin, less oxygen, more shortness of breath. This thickening of the wall gets what we call an increase in the resistance, leading to right side heart failure. About 15 years ago, there was a paradigm shift in the understanding of pulmonary arterial hypertension thinking, why do these patients have a thickening of their wall? It's because there is proliferation of endothelial cells, smooth muscle cells like neoplasia, like a tumor. Maybe if we block this progression, this proliferation, we may stop the disease and maybe even regress the disease in making the wall thickness less thick and smaller. Therefore, about 15 years ago, there was a very interesting clinical trial with a drug called Imatinib or Gleevec. Gleevec has, for patients with chronic myelocytic leukemia has been a revolution. Patients with CML in the past needed to have a bone marrow transplant. With the administration today of Gleevec it’s been a revolution and patients can live with CML, with this chronic myelocytic leukemia for years and years with absolutely no progression of their disease. Similarly to CML, the idea was maybe if we give an agent like Gleevec or Imatinib to these patients, we may stop the proliferation of endothelial cell and smooth muscle cells in the wall of the vessel and stop or even regress the disease. This trial, called IMPRES, was done about 13 years ago. The results of the study were absolutely beneficial. However, more than 30% of patients quit the study because of side effects, and also patients on anticoagulation, on blood thinners developed some intracranial hemorrhage. The FDA, because of the side effect, decided not to approve this drug for pulmonary hypertension. Just to give you a background that there is really a paradigm shift in the understanding of the disease. The new drug that has recently been approved by the FDA is being called sotatercept. That's another mechanism. We know that in our system, every cell has like a yin and a yang. There is activin, a system which stimulates the gene while the bone morphogenetic protein system is slowed down. The activin slowed down the proliferation of cells. In our system, in a normal system, you do have a balance between BMP and activin. We also know in patients with pulmonary hypertension, they do have too much activin. This new medicine, sotatercept blocks the activin. Activin is like an accelerator. It does promote proliferation of cells on the gene. If you block the activin, you recalibrate the BMP and the activin, reducing this proliferation of cells. Sotatercept was shown really to improve patient pressure as well as improving their six-minute walk distance as well as their quality of life. Sotatercept has been approved by the FDA for the last year and really has changed the field of PAH. Another group similar to the Gleevec, but as I said, Gleevec was not approved by the FDA because of the side effects. The idea was maybe if we could give a Gleevec as an inhaler without systemic effect, patients would absorb the drug into the lungs without having any side effects. There was a clinical trial with inhaled imatinib, inhaled Gleevec if you want. Unfortunately, the study was not positive, because most likely Imatinib was not absorbed by the lungs. However, another company was able to produce a super imatinib, which is being absorbed by the lungs called GB002 or showing a significant improvement in the pressure, as well as the PVR. Currently, there is a with this drug as an inhaler. So, in summary, I just want to say the drugs we have currently until now were vasodilators, they do slow down the progression of the disease but don't stop the disease. Now, we do have one drug approved by the FDA. Hopefully, a second one will be approved. These two drugs stop the proliferation that occur in pulmonary hypertension and hopefully will stop the disease and potentially even regress the disease. We are getting closer to maybe a cure of the disease with agents like sotatercept and . Thank you for listening. My name is Ron Zolty and I'm aware that my patients are rare. Learn more about pulmonary hypertension trials at . Engage for a cure: #phaware Share your story: Like, Subscribe and Follow us: . #phawareMD #clinicaltrial #PROSERA /episode/index/show/phawarepodcast/id/35842570

Episode 516 - Ron Zolty, MD 04/14/2025

Rajan Saggar, MD - phaware® interview 515 04/08/2025

Rajan Saggar, MD - phaware® interview 515 For decades, researchers have sought better treatments for pulmonary hypertension in interstitial lung disease, a condition that drastically impacts patients’ quality of life. In this episode, Dr. Rajan Saggar dives into the latest advancements, including new inhaled medications, upcoming clinical trials, and the push for more personalized treatment approaches. This Special Edition episode is sponsored by and . I am Dr. Rajan Saggar. I'm Co-Director of the Pulmonary Hypertension Program at UCLA, and my Co-Director is Dr. Richard Channick. We work at that program together. One of my main interests, actually, is pulmonary hypertension, complicating interstitial lung disease. Sometimes, interstitial lung disease can progress and become pulmonary fibrosis. So, along that spectrum of disease, pulmonary hypertension, which is Group 3. There's basically five types of pulmonary hypertension. There's five different groups. The one related to lung disease ... and again, that lung disease could be COPD or emphysema, or it could be interstitial lung disease - pulmonary fibrosis. Any type of lung disease is considered Group III pulmonary hypertension. The focus that we have right now is specifically with patients who have interstitial lung disease or ILD and pulmonary fibrosis. This is a field that I've been interested in for a couple of decades. There's been a lot of failed studies over the years. There's been a lot of attempts to use drugs that have clearly worked and are now FDA approved for the much rarer form of Group 1 pulmonary hypertension, which is also called pulmonary arterial hypertension. Those drugs, which are now FDA approved and thriving and doing well have been used or tried to be used in the Group 3 pulmonary hypertension setting. Unfortunately, the majority of them have failed. But the good news is recently, as of April of 2021, there is a medication that now is FDA approved, specifically pulmonary hypertension in the setting of interstitial lung disease or what we call PH-ILD. That is inhaled treprostinil. It's an inhaled medication that's taken four times a day. What's exciting now is that that started off a chain of events, which I think re-lit interest in this type of pulmonary hypertension. Now, there's several pharmaceutical companies that have shown interest, and more than that, have actually started clinical trials looking at the potential for other inhaled therapies. I say inhaled, because most of the therapies being looked at are inhaled therapies. The rationale there being you have a lung disease, specifically affecting the lung and you happen to have associated pulmonary hypertension. The idea being that if you inhale something as opposed to taking something orally or something through the vein, you might have more of an effect. You're delivering the drug to the area of interest. There's a lot of people and rationale for doing that and maybe sparing patients from the side effects of these drugs, when you inhale it, as opposed to giving it what we call systemically, either orally or through the vein. There's a lot of interest in the inhaled approach. Another product being looked at, and the reason I'm bringing it up is it's maybe close to being available and being launched, is a drug called Yutrepia. Again, another formulation of inhaled treprostinil made by a company called . We are recording this before the potential for launch, but it's possible that this drug could be launched as early as May of 2025. Again, the potential benefits of that drug, because one could ask, "Well, what's the point? You already have an approved medication that's inhaled treprostinil, as well." The touted benefits of that drug may be a decrease in side effects, particularly cough, which may allow more up-titration of that particular medication in terms of actual absolute dosing. What we do know is that more is better of this medication, inhaled treprostinil, in the setting of PH-ILD. If we can get to higher doses without having side effects, that would be the ultimate goal. Then, even a further goal would be to do that with, let's say, once a day dosing, for instance, to make the frequency less. That would be pie in the sky. But the point is there's motion here and there's movement, so we look forward to that. There's another formulation of inhaled treprostinil being looked at, which is by a company called Insmed, and they're also looking at a once-a-day formulation of inhaled treprostinil. Again, specifically in pulmonary hypertention with interstitial lung disease. That's not as far along as the Liquidia product, but that's also exciting, because again, you would be going to once a day, which would be a game-changer for a lot of patients. There's other companies looking at other formulations of inhaled treprostinil and trying to make that better, if you will. The reason I say that is because the current approved medication, inhaled treprostinil, is a drug which is four times a day and also can have cough associated with it, which is not atypical for an inhaled medication, but a lot of these patients have cough even from their interstitial lung disease to begin with. So, when we introduce a medication which sometimes exacerbates their pre-existing cough, it can become quite difficult. At four times a day, it can be a little cumbersome. There are other companies trying to improve the side effect profile perhaps, but also the frequency of how often they take it, trying to build on what's already out there. In addition to reformulating the treprostinil product there, there's also other companies looking at other mechanisms, just brand-new mechanisms. For instance, there's a drug called , which is made by . This is a drug also inhaled, a dry-powdered inhaler, which blocks certain molecules in the body called tyrosine kinases. It blocks several of these and has a lot of promise in PAH, so that's Group 1 pulmonary hypertension, but they've extrapolated that and now are looking at it actively in Group 3 pulmonary hypertension, specifically this PH-ILD, pulmonary hypertension with interstitial lung disease. That's exciting. The other medication that's being looked at is a drug made by , which is called , which is reminiscent of another pulmonary hypertension medication that we have in Group 1 disease, which is called Riociguat. But this is specifically being looked at, much like the Seralutinib product is being looked at in both Group 1 pulmonary hypertension as well as Group 3 pulmonary hypertension. Again, specifically pulmonary hypertension with interstitial lung disease. So again, you can see that the people are making newer medications not just for the Group 3 necessarily, but they're looking at it in Group 1, the more traditional pulmonary hypertension, the pulmonary arterial hypertension, but also looking at it in Group 3 pulmonary hypertension. That product with Pulmovant is also an inhaled medication. There is a protocol in motion, as we speak, looking at PH-ILD, which is exciting. It's a guanylate cyclase activator. It works in the nitric oxide pathway, which has been an old pathway used in pulmonary hypertension. It has some interesting benefits that are touted in terms of how it works in that pathway specifically. But without getting into the details, it is an old mechanism, but looking at it with new parts, if you will. That's Pulmovant. Again, that's their new medication, Mosliciguat. That's out there, as well. There's some other ones in the pipeline that are not as far along. There is a aldehyde dehydrogenase stimulator, which is being looked at. Again, very early. There's a drug that blocks hyaluronan synthesis, which is a drug that's coming out of Stanford actually, which is also very early in the mix. Nothing really ready for patients to engage in just yet. But again, the pipeline's pretty deep. It's very exciting because pulmonary hypertension with interstitial lung disease has really been a type of pulmonary hypertension yearning for a drug that we can actually give patients and actually get some relief. It turns out that this particular type of pulmonary hypertension, it causes a lot of illness, much more than the other types of pulmonary hypertension. These patients are unfortunately dealing with pretty much two lung diseases, they have pulmonary hypertension and they have this interstitial lung disease, so they tend to need oxygen. They tend to be very functionally limited. As anyone knows, living with oxygen in the house is hard enough. Leaving the house with oxygen, it becomes extremely difficult. Unfortunately, us in the respiratory world and the pulmonary world, we haven't really figured out how to best give oxygen outside of the house just from a comfort standpoint, and just making it easy for patients. It's still, I think, relatively cumbersome. I think that's another area that we should be focusing on to make living with oxygen easier, particularly outside of the home. So yeah, I'm happy to report that there's a lot going on in this field. From a clinical trial standpoint in the PH-ILD space, luckily so far, knock on wood, there's been sort of minimal overlap in terms of the trials being available. In other words, we don't have two trials or more going on at the same time for PH-ILD. For instance, I mentioned the Liquidia product, Yutrepia is farther along, so their study is finishing while the Pulmovant study with Mosliciguat is ramping up. So luckily, we haven't had the problem of having to try to figure out which study to go into, or which one to consider, or having choices in that matter. That really hasn't happened just yet, but I suspect it will, given the pipeline we just discussed. At that point, I think it's just an individual patient discussion, one-on-one discussion with the pros and cons, and probably has a lot to do with the side effects they're dealing with at some point, or inclusion/exclusion criteria. I think it gets into some of the details that we'd have to have an individual discussion with that particular patient to make the best decision with them. From a physician standpoint and trying to understand disease, any disease, not just pulmonary hypertension with interstitial lung disease, once we get more and more into it, we often start realizing that things can't just be lumped. Patients can't just be lumped into one category that you have PH-ILD and everyone will respond to drug X or drug Y. We all know that not everyone responds to available therapies. Or if there is response, there's a spectrum of response. Some are no response, some have mild response, some have significant response. But what makes this even more, I guess in some ways, difficult, but also exciting from a medical standpoint is that we are learning that there is an extreme amount of heterogeneity within PH-ILD. By that, I mean there's so many different causes and etiologies of ILD, and each of those patients with ILD has a different natural history of that specific ILD in terms of how it progresses. Some people are much more stable than others. Some people are progressively getting worse faster than others, and it has a lot to do with the type of ILD. Then, when you throw the pulmonary hypertension on top, the pulmonary hypertension itself has a heterogeneity to it in terms of how it progresses. Does it stay stable or does it tend to progress? Then, you can understand that when you're dealing with two diseases which are heterogeneous in their natural history, then it becomes a little bit more difficult to understand in terms of lumping people in one category. That's important, because the physicians in this space, and I being one of them, one of our tasks is to make sure that we understand what we call phenotypes. A patient's phenotype is not always the same with PH-ILD. Phenotype means the set of characteristics specific to that patient. There'll be patients just like that patient that fit into a certain phenotype. There's going to be multiple phenotypes in this PH-ILD space. We're learning about those. The reason it's important is because not only do they have different rates of progression or changes in their ILD and PH, but it also predicts who's going to need a lung transplant sooner perhaps, or who may be more responsive to a medication. Perhaps a patient who has idiopathic type of disease responds better to something than someone who has a connective tissue disease or vice versa. Those are the things that we need to learn about, so then we can inform patients better. Sometimes, that might trigger us off into saying, "Hey, you probably should think about this clinical trial, because the data with your type of phenotype may not be as predictable or as wonderful as we want." That's just the reality of the situation. Some people are going to have better responses than others. But that's important for us to identify that a priori so we can actually have a discussion with some real data so the patient can be informed, so we are not just making up stuff. We want to actually have real data, that hard data so we can actually help the patient make the best decision. I think that's really important. I'm Dr. Rajan Saggar, Co-Director of the Pulmonary Hypertension Program at UCLA in Los Angeles, California. And I'm aware that my patients are rare. Learn more about pulmonary hypertension trials at . Engage for a cure: #phaware Share your story: Like, Subscribe and Follow us: . #phawareMD #PHILD #PROSERAstudy #clinicaltrial #PHOCUSstudy /episode/index/show/phawarepodcast/id/35843325

Episode 515 - Rajan Saggar, MD 04/07/2025

I'm Aware That I'm Rare: the phaware® podcast

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