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

Eric Borstein - phaware® interview 536 09/03/2025

Eric Borstein - phaware® interview 536 A 200 Mile Journey from LA to San Diego to Raise Awareness for PH When Eric Borstein collapsed in his bedroom in 2020, doctors gave him just months to live. Instead, he fought back with walking, mental health, and the support of his community. Now, he’s leading a movement, raising hundreds of thousands for pulmonary hypertension research, and walking 200 miles down the California coast to prove hope has no limits. Learn more about the September 7, 2025 Steve Van Wormer: Welcome to I'm Aware That I'm Rare: phaware podcast. I'm Steve Van Wormer from Phaware Global Association. I'm here with Eric Borstein, a patient who you may recognize from the podcast who did an episode with us last year. Eric lives in Los Angeles. He's a pulmonary arterial hypertension patient diagnosed in 2020, and he's got some exciting updates to what has happened in his life since the last time he appeared on the show over a year ago. Eric, thank you so much for being here today. Eric Borstein: You're welcome. Thank you, Steve, and thank you for having me back. Steve Van Wormer: Last year you did a walk called, " Basically, you walked from Santa Monica to San Diego over the course of a week. Before we get into that, I wanted to see if you could give viewers the overview of what happened to you back in 2020 that led you to that first Where is EB walk. Eric Borstein: So, September 21st, 2020, I collapsed in the bedroom and almost died, was taken to St. John's Hospital here in Santa Monica where I was stabilized and was diagnosed with Class 4 pulmonary arterial hypertension. I had collapsed from severe right ventricular heart failure. After a few days and being stabilized, I was transported to Cedars-Sinai and I spent a total of 16 days in the ICU. (Doctors) told my wife I had three to six months to live. I didn't know any of this. I had made a decision very early on that I was going to beat this disease, and I didn't know what that meant. But I looked my wife straight in the eyes, tears rolling down my face, and said “I'm going to beat this disease,” and she had tears rolling down her face and she said, "I know you will." But I didn't know how sick I was. I came home and started walking, which helped mitigate those side effects (of the medications). A block turned into two, turned into three, eventually a mile, and two and three. Walking just became a big part of my life. I also, very early on, started talking to a psychologist and realized that living with a terminal disease like PAH, positive mental health was very important. So, through positive mental health, exercise, strict nutrition, and relying on family, friends, my neighbors, my community, what I call my "village", I've made nothing short of a miraculous recovery. I was put on a pump. They never thought I would get off the pump. After a year, my right ventricle made almost a complete recovery and I was taken off the pump. I've been on oral medications ever since. Obviously, there's no cure for PAH, so I live with it. But I've adopted this, what I call "pieces of my pie", which again are medicine, positive mental health, nutrition, exercise, and my village. That's what I live by. Now that I'm better, I'm feeling better, I've dedicated my second part of my life not only to my health and my family, but to advocacy and raising awareness for the disease, and then also for people underprivileged who need it most. When I was diagnosed with PAH, we have a family foundation and we got involved with National Jewish Health in Denver, and we got involved with funding research. This is a disease that nobody in my world had ever heard of before I was diagnosed. We looked around the country, found NGH. On one visit back there, about probably three years ago now, I was introduced to Patty George who was one of the founders of Team PHenomenal Hope. They said, "You've got to meet Patty." We met and her energy was infectious. The mission that the organization had aligned with the lifestyle I was living. Right around that time, my oldest daughter came to me and said, "Dad, I want to do a fundraiser for the disease that you live with," and Where is EB was born. What better organization to raise the money for than Team PHenomenal Hope? I thought, okay, let's do a walk. So, we did a 5K walk and fundraiser, and I'm like, you know what? What better way to raise awareness for a rare disease than to go big? I planned a walk from LA to San Diego. A 170 mile walk. I would go down the coast, end in Del Mar. So, we started planning Where is EB, and what I thought would be 150 people coming out to a walk, maybe we would raise $75,000 through friends and family and people that we know. We raised close to $200,000 all for PH, PAH research and helping provide for people living with the disease that need it most. The first Where's EB I walked from, like you said, Santa Monica. We headed down the coast. Once we hit Huntington Beach, I just went down pretty much Route One. The biggest hurdle was Camp Pendleton. It turned out through the help of Carl Hicks, another board member, but somebody who I've become very close with. It's a very close-knit community because the disease is so rare and I've met so many amazing people along the way. Carl, who lost his daughter, Meagan. Ashlee Gambino, who I had the privilege to meet on a trip back to Las Vegas, who's a patient who has just an amazing story. And I met you and I learned about your story with Lucas. It is just such a tight-knit community, because when you're touched by this disease, whether it's losing a loved one or, like myself, being a patient, it is a family. So, Carl helped us through Camp Pendleton. That was a big hurdle because you can't go from LA to San Diego without going through Camp Pendleton. The US Marines could not have been more supportive. That day, going through Camp Pendleton was the highlight of my week. I was being escorted by the Marines. They brought in somebody to do an interview, and I'm being interviewing and we're walking, and I share my story. The interviewer stops and he looks at me and he said, "Sir, can I ask you a question?" He said, "Are you a Christian?" I knew immediately why he was asking me this. I said, "I'm not, but what I can tell you is I was given a second chance in life, and that second chance was to provide hope for those who need it most." He stops, and I'm abbreviating the story, but he puts his hand on my shoulder and he said, "Sir, that's probably one of the most meaningful things I've ever heard in my life, and that transcends all religion. Thank you." I realized right then and there that by sharing my story and by doing Where is EB and raising awareness for the disease, you never know who you're going to help. So, we get through Pendleton. I'm with Hap Farber. He was accompanying me by bike down the coast. Hap is another Team PHenomenal Hope board member, an expert in the field, and has become a friend. We probably got into the Del Mar area, and I had already calculated. I'm feeling great, there's no way we're going 175 miles. In Hap's head, he already had figured this out. He had already gotten to know me. Because I was pushing the whole way, and I'm living with PAH. Here I am pushing going down the coast, and we get into Old Town San Diego, and we go to bed and we wake up and I turn to Hap and I'm like, "We're not going 180 miles." He goes, "I know. We're going 200." So, we ended up going all the way down to Imperial Beach, if anybody knows Southern California. Almost down to the border. We were like three miles from the border. Came and then went up through Coronado, ended in Del Mar. It was 202 miles in six and a half days, all raising awareness for PAH and PH. That was last year, last September. The story just started to take off. I've met some amazing people along the way, developed relationships with people along the way, and it's evolving. It's evolved into a movement, is what I call it. I couldn't be luckier. People ask me, they say, "Do you have any regrets through this whole process?" I realized that I put people through some hardship in those years leading up to collapsing. I knew I was sick, but I wasn't going to the doctor. I was afraid to find out what was wrong, and I learned later on from my psychologist that upwards of 75% of men who are very sick don't go to the doctor. So, I wasn't alone. But I wasn't going to the doctor, and it was really creating hardship in my family, and for my wife and my kids, and it was creating issues in the house. Through the whole process, I have two regrets. One is that I put my family through that in those four or five years, because living with PAH is very alienating. You can be surrounded by 20 people, but you're alone because you're suffocating. That was one of my regrets. My second regret is that one of my kids saw me collapse, and then my second daughter... It was during COVID, so everybody was home, and my second daughter came up and sees me lying in a pool of blood. That is the hardest thing for me and that is my biggest regret. But besides that, I tell people if it didn't happen so dramatically, with stress that was going on in my life I might've been still dealing with that, but maybe I solved my health issues. But not everything would've been resolved. When I collapsed, it was like breaking through a sheet of ice. Everything went away. All problems, all stress, anything I was dealing with. I decided right there and then I was going to get help, I wasn't going to die, and I headed down a completely different path and I haven't looked back. That's my only regret. The last year has just taken on this amazing life of its own. I look at this as a second chance. So, through speaking engagements and then this very special project that we're now working on. I was approached about doing a full feature documentary and hired an amazing production company who's both familiar with obviously very good at documentaries, but also familiar in the rare disease field. It's owned by a woman by the name of Christie McCaffrey, amazing person, mom. She lost her mom to scleroderma, so she understands rare diseases. We're working on this amazing film. It's going to educate people on PH and it's going to educate people on PAH, but it's really a movie about overcoming adversity and providing hope, and through the adversity, what people do. It's going to feature myself and my story, but it's bringing in Carl Hicks and he's going to share his story, it's going to bring in yours truly (Steve Van Wormer), and it's going to bring in Ashlee Gambino. It's going to share their stories, but it's going to share what each individual has done through their adversity, through their moment and what they've done with it. The hope is that it educates people on the importance of mental health, and village, and education, and exercise and diet. But really for anybody going through adversity, whether it's living with a rare disease, losing a home in a fire, going through a divorce, losing a loved one, being diagnosed with anything, taking that first step and utilizing these tools, and how have we gotten through it and what are we doing with it? We've all decided to take that first step in our own way. My hope is by sharing my story and sharing these other stories that other people can see that and they can see if we can do it, they can do it. So, that's a really special project that I'm working on. Then, we're putting together the second annual Where's EB? That's going to be on September 7th. After the event, after the 5K, which is going to be an amazing, fun morning with food and giveaways and music and speakers, everybody's going to bid me adieu and I'm going to head down the coast again and walk 200 miles in six and a half days from LA to San Diego, and we're going to do it all over again. All with the hopes of raising as much awareness for the rare disease that I live with, which is pulmonary arterial hypertension and pulmonary hypertension. Steve Van Wormer: It's interesting, when you describe what happened to you five years ago, when you decide to pick yourself up and to move forward, whether you be the patient in your case, or a care partner, or whatever it is, a spouse of someone inflicted by this disease, can you tell me a little bit about how in your brain you kind of go from this selfish to selfless kind of role? If that's an accurate portrayal. I feel that for myself, and it's just like how you are pulling at threads in the community, and relationships, and people, and being blessed with having access to doctors and other patients and support and all that. How do you reconcile that in yourself? Just in your daily life or when you're singularly walking the streets or the highways of Los Angeles halfway to San Diego. Eric Borstein: Helping others came naturally to me. I have a philanthropic background. It was instilled in my brothers and I very early on that we're fortunate, and because we're fortunate, we should give back. It really wasn't a choice. We're going to give back. I've always volunteer coached. Even before I had kids I volunteered places. So, I always gave my time even before I had the means to give and help others financially. I've also been a very outgoing person. We always had people over at our homes. I always wanted to be around friends. I was just a very upbeat, outgoing, friendly person, giving person. So in those, I'll call it the four years, five years leading up to collapsing and pulling away, other than suffering health-wise and it getting worse and then to the point where I couldn't walk and breathe, the hardest thing was pulling back and it sent me into depression. I was depressed. I didn't see it. My wife saw it. But I was depressed. Now looking back, it's because I wasn't me. That was a really difficult time, and I'm the least selfish person you'll meet naturally. I give. I don't like to take, I give. I didn't understand it going through it, but one of the reasons why I was becoming depressed was because I wasn't myself. I wasn't happy. I wasn't wanting to be with people. I was really pulling back. After I collapsed and I was stabilized and I was able to start to look out for others again, it was just so easy and natural to want to help others. Sharing my story was very therapeutic, and to this day is very therapeutic for myself. It helps me. It is a reminder of where I've come in such a short period of time when I'm able to tell people I just walked 30 miles today. Living with a disease is very difficult. People look at me and they're like, "You look great." But it's a grind. It is a grind living with PAH. It's every day you've got to deal with really bad side effects. Again, one of the main reasons why I walk. You deal with the fact that you're going to live with this disease for the rest of your life, as long as you're alive. In the back of your mind it's always there. Are my lungs going to fail? Is my heart going to fail? It's always there. So, it is a battle. It is a daily battle both mentally and physically. But when I was able and I was healthy enough to help others, it was just very natural. It's something that's just in me. It's something that is very important to me. When I realized that my story was touching people both inside and outside of the PAH and PH world, it's something that I feel is my responsibility. I am very fortunate that I'm able to dedicate my life to my health. I'm very fortunate that I have an amazing business partner that takes on most of the day-to-day operations of our business. I'm fortunate that I've got the best doctors, and I've got great insurance, and I can afford the co-pays, and I can have a psychologist. I am very aware of that, but I'm also very aware that most people aren't so fortunate. Especially in the rare disease world, there's just not a lot of attention and dollars at the national level spent on these diseases, and the underserved are underserved. I feel like it's my duty to help those. It's my duty to provide toward research to hopefully find new therapies and extend lives. I've rededicated the second part of my life not only to myself and to be as healthy as I can, and to my wife and kids and those around me, but to help those others that need it most and to raise as much awareness for this disease as I can while I'm here. Steve Van Wormer: For me, I feel I was always very lucky. We were always very lucky, my wife and I, with our son, Lucas. He was diagnosed relatively early. We had great access to insurance. We had good doctors. And so, when you find people, when you know there's people in the community that don't have that access to services or they can't afford a clinic or they're just lost in the wayside... Right? I think that finding people like yourself, like Carl Hicks, another great friend I've known for two decades, that especially ones that have lost somebody, I feel like it would be easy to kind of just let the next generation figure it out. But I think this disease in particular is really built on the backs of all the families and community and the doctors that came before it. You mentioned this other patient, Ashlee Gambino. She's someone that's going to be a speaker at a December conference that's being held in Boston. So, the listeners have not heard her story yet, but they will. But it's another powerful story of a patient who went through a lot of tragedy, and has really picked herself up and is really working to help herself, first and foremost, and helping many others beyond that. Eric Borstein: One of the things that I've found being a patient, another highlight of my year this past year was I was invited to go to Washington on World PH Day, and meet with Congressional Delegates and meet with US Senators and their offices and staff, and share my story, and advocate for hopefully no cuts to NIH funding, Medicaid and the like. With everything going on, I felt, again, it was so important to do that, and it was a highlight of my year. What I'm finding in moments like that, I was elected Board Chair of Team PHenomenal Hope this year, and being an advocate for the disease and through Where is EB, what I'm finding is because I'm a patient and I'm living with this disease and this disease almost took my life, it's a different perspective but it's a very effective perspective. It's something that I don't take lightly. Again, yourself included, Carl, amazing advocates and voices for the disease. Ashlee, she struggles. She's much more newly diagnosed, and she'll share that in her story, but we're at different stages. But because I am able to, again, I feel it's important and it's effective being a patient. My livelihood depends on these things. My livelihood could depend on the next therapy, and those therapies come from NIH funding, and they all start somewhere. Being that patient voice is something I don't take lightly and something that I'm really embracing. Again, I've always been passionate about philanthropy, and I sit on other boards and all of them are so important. But living with this disease and advocating for this disease is something that I've never felt so passionately about. Steve Van Wormer: That's wonderful. We are blessed to have you. I think we would be remiss if we didn't say, and I trust you would agree, that a patient specifically who might be listening to this, while neither of us are doctors, the importance of pulmonary rehab and all that is a good thing. But I think we should tell patients, if you're inspired by a person like yourself, Eric, they should definitely talk to their healthcare team before embarking out on doing walks and all that stuff. Mental health on the other hand, I would say that's a pretty large part of your pie. Would you agree? Eric Borstein: It is. I tell people I wouldn't be alive without the medications, obviously. I'm extremely lucky that my body reacted so quickly to the medication that I was on. That's number one. Then... /episode/index/show/phawarepodcast/id/37892885

Episode 536 - Eric Borstein 09/02/2025

Akshay Muralidhar, MD - phaware® interview 535 08/27/2025

Akshay Muralidhar, MD - phaware® interview 535 Dr. Akshay Muralidhar, Co-Director of the Pulmonary Hypertension Center of Excellence at Arizona Pulmonary Specialist in Phoenix, discusses the importance of having a specialized center for pulmonary hypertension. Dr. Muralidhar also highlights the challenges of managing patients with substance abuse issues, particularly methamphetamine use. Dr. Muralidhar emphasizes the importance of access to care, particularly for underserved communities, and the need for outreach programs to ensure that all patients have access to treatment options. This Special Edition Episode Sponsored by: My name is Akshay Muralidhar. I am a Co-Director of the Pulmonary Hypertension Center of Excellence at the Arizona Pulmonary Specialist in Phoenix, Arizona. I joined this group in 2019. We have been a Center of Excellence for nearly a decade now. We have been managing and caring for pulmonary hypertension patients in the Phoenix area for almost two decades, managing complex care across the spectrum of pulmonary hypertension disease process. I did my training at the University of Colorado at their Pulmonary Hypertension Center of Excellence. I graduated in 2019. I am a native of Phoenix, Arizona. I was brought up here. I was looking for a reason to come home. It was a nice coincidence that my passion was explored more here at the Pulmonary Hypertension Center of Excellence at Arizona Pulmonary Specialist. The importance of having a pulmonary hypertension center of excellence is something that I really felt deeply about, and that's something I looked for when I wanted to start my career as a new attending and a new graduate of a fellowship specialty in pulmonary hypertension. So what makes a pulmonary hypertension center of excellence important? Pulmonary hypertension is a rare disease in the general population, but is an incredibly complex disease requiring multidisciplinary care across a spectrum of organs in the human body. As anyone who suffers from pulmonary hypertension knows, the one effect of worsening pulmonary hypertension can affect every single organ in the body. The specialty care offered by a Pulmonary Hypertension Center of Excellence, I feel, really allows for that multidisciplinary comprehensive care that a pulmonary hypertension patient needs with the expertise of someone who has seen hundreds of patients with pulmonary hypertension. That is important because being a rare disease, pulmonary hypertension sometimes gets overlooked or is difficult to diagnose in patients who might present with what we call non-specific symptoms. These are symptoms that don't really tell you what the disease is, but are damaging and tend to affect patients significantly, such as shortness of breath, leg swelling, lightheadedness, symptoms often experienced by pulmonary hypertension patients. It takes an experienced diagnostician and management specialist to be able to correctly diagnose disease and manage it in the future. Pulmonary hypertension is a disease of the right side of the heart and the lungs themselves, which results in damage to the right heart and the pulmonary vasculature that goes to it. When people present with shortness of breath, leg swelling, and chest pains, oftentimes routine testing in the hospital or at your general cardiologist or general pulmonologist office involves an echocardiogram. This often shows severe dilation and dysfunction of the right ventricle with potential involvement of the elevations in pulmonary pressures. In that situation, people often get alarmed about the presence of pulmonary arterial hypertension. While it is important to be concerned about this, it is also important to take the next step in beginning diagnostic testing and the referral process to a Pulmonary Hypertension Center of Excellence. The reason for this is because uniformly pulmonary arterial hypertension was a fatal disease in the 1990s. Thanks to expert care and expert medication and treatments, it is now well managed and completely treatable if the diagnostic tests indicate pulmonary arterial hypertension. The most important thing is having a low threshold for suspicion. Whenever we see patients with evidence of right heart failure, which include leg swelling, shortness of breath, lightheadedness, things of that nature, we have a low threshold for getting an echocardiogram just like any general cardiologist, pulmonologist would. If there's evidence of right-sided heart failure, a referral would be indicated to a pulmonary arterial hypertension center. In our center, we will do additional diagnostic testing and screening questions to be able to identify potential causes for this and then do confirmatory testing with right heart catheterization, which is the diagnostic test of choice to determine if the patient has pulmonary arterial hypertension. That allows an experienced physician to be able to formulate a management plan based on the severity of disease and the experience the patient is having. At a Pulmonary Hypertension Center of Excellence, the goal is to provide a comprehensive care management strategy for the patient. This includes appropriate diagnostic testing, determination if the patient truly does have pulmonary arterial hypertension, and then classification into one of several groups of pulmonary hypertension that are currently described including: Group 1 pulmonary hypertension, which is pulmonary arterial hypertension, Group 2 pulmonary hypertension, which is due to left heart disease, Group 3 pulmonary hypertension, which is due to lung disease and hypoxia, Group 4 pulmonary hypertension due to chronic thromboembolic pulmonary disease and Group 5, which is pulmonary hypertension due to other etiologies. Now, any experienced pulmonary hypertension physician will tell you that many patients fall into multiple categories. In this case, it takes an experienced physician to determine which is the predominant factor that is affecting the right heart in the pulmonary vasculature, and to be able to identify appropriate treatment strategies. Treatment strategies vary depending on the type of pulmonary hypertension you have. That is why it is very important to make sure that patients have appropriate diagnosis and classification of their disease process. After this, a comprehensive strategy to determine treatment is indicated. This includes meeting with an experienced nurse coordinator to be able to assist with management strategies as well as close follow-up routine lab testing to determine how treatment is progressing. If treatment involves therapies such as continuous infusions or injections, appropriate training is necessary to make sure that our patients are able to manage their disease properly as well as the side effects. As many patients who suffer from pulmonary hypertension know, side effects from medicines often are just as bad if not worse than the symptoms of the disease themselves. It takes very important coaching by experienced clinicians and nurse coordinators to be able to manage the side effects of the medications so that patients are able to take them without too much discomfort. Over time, many of these side effects are manageable and the true benefit of these medications are observed in the appropriate patient. Furthermore, being able to determine which classification of pulmonary hypertension a patient has is important, because medications that work for some groups of pulmonary hypertension such as Group 1 and Group 4 disease, may not work for other groups of pulmonary hypertension such as Group 2 disease. It is extremely important to have an appropriate interview with a pulmonary hypertension trained physician to be able to determine which classification predominates. When Centers of Excellence are identified, patients have been referred to us from all over the state and sometimes even across the country. I've had patients from rural Arizona, which is a large swath of area as well as many Native American reservations. I've also seen patients from Southern Nevada and Western New Mexico who make the sometimes eight-hour trek to get to our center. So, we have a very large referral basis to be able to seek a Center of Excellence so that they can get comprehensive care for their pulmonary hypertension patients. Outreach is incredibly important for any Center of Excellence dealing with rare diseases such as pulmonary hypertension, because it is very important to identify those that don't have access to care, to be able to get them to a Center of Excellence in an appropriate and timely manner. I personally do a month of pulmonary clinic at one of the Native American reservations. While it is a general pulmonary clinic, I've already identified several pulmonary hypertension patients in that area that I have then ensured that they are seen and managed by our Comprehensive Center of Excellence. It's incredibly important that not only common diseases, but also rare diseases that are life-threatening such as pulmonary hypertension be identified with a low threshold for referral and ensuring that these patients have the appropriate resources to be able to do that. Pulmonary hypertension centers, as I mentioned, also provide a comprehensive management strategy to these patients. This not only includes access to nurse coordinators, physicians who are trained in pulmonary hypertension such as myself, but also access to things like support groups as well as symposia and learning materials and access to online materials that are important for patients to be able to take away and manage their disease at home. Methamphetamine use is one of the most common drugs used in Phoenix, Arizona. In fact, Phoenix has unfortunately topped the charts in the country for methamphetamine use. Many of our patients who struggle with methamphetamine use get admitted either to the hospital with decompensated previously undiagnosed pulmonary arterial hypertension, or are seen in our clinic for progressive shortness of breath and are then found to have pulmonary hypertension. This is a particularly difficult population of patients to treat only because not only do we have to manage their medical disease as well as ensure that medications are administered appropriately, but we also want to address their ongoing substance abuse problem in a timely manner. Unfortunately, resources in general are lacking from management of substance abuse such as methamphetamines. So, a comprehensive care is only benefited many of our patients because of close follow up management strategies, support groups, things of that nature that really allow our patients to understand the lethal disease that they have because of their substance abuse problem and seek treatment before it's too late. Pulmonary hypertension back in the 1990s was a uniformly fatal disease. Thanks to the development of IV therapy, specifically IV Epoprostenol, this started saving lives initially. Since then, thanks to the advent of clinical trial research programs, pulmonary hypertension is now an extraordinarily manageable disease. It's wonderful to see the advent of therapies available for pulmonary hypertension patients thanks to clinical trials. Part of being a Pulmonary Hypertension Center of Excellence is that we have a robust clinical trial program. We understand the importance of clinical trials in improving the nature of treatment for patients suffering from pulmonary hypertension. Our patients are wonderful in actively participating in clinical trial programs. Thanks to these, we have now been able to administer adequate treatment for pulmonary hypertension to many patients that just consist of oral therapies. Thanks to clinical trials, a recent drug, Sotatercept, was approved, which is a new first-in-class drug that has been shown to be beneficial for pulmonary hypertension patients, and the field is only expanding. We have many partners in our pharmaceutical industry as well as in the clinical practice arena that developed a partnership with Centers of Excellence across the country thanks to being able to bring together many patients from a rare disease. In order to have a successful clinical trial, you need to enroll many patients and need to be able to demonstrate that your particular therapy has benefit to these patients. In a rare disease, the only way to be able to do that is to focus on centers that see these patients on a regular basis such as Pulmonary Arterial Hypertension Centers of Excellence. So, we personally have a robust clinical research program. We've been involved in most clinical trials that have come in the last decade, and ours the highest enroller in many of these as well thanks to an excellent clinical research team and most importantly, our amazing patients who are willing to participate in these trials so that they can benefit the field as a whole. One of the biggest reasons why I joined a Pulmonary Hypertension Center of Excellence is because I am able to open the door to patients who are interested in expanding treatment options for the field so that everyone can benefit by participating in these clinical trials. Being part of a Pulmonary Hypertension Center of Excellence, I think it is very important to make sure that patients have appropriate strategies in place for the therapy. This not only involves diagnosis of the disease, but also appropriate risk stratification. Many of my patients fall squarely into the category of pulmonary arterial hypertension, but many others have comorbidities that put them across several groups of pulmonary hypertension. All these patients require a specifically tailored regiment of therapy that allows for simplicity of management so that patients know what they're taking, how they're taking it, and to make sure that they're able to take it appropriately without overdoing it in terms of therapy. The advent of oral and inhaled therapy and now with Sotatercept has really made a difference in terms of being able to simplify the regimen. However, some of our sicker patients, while they require multiple therapies, 1, 2, 3, or even four therapies now with Sotatercept, many of our patients do just fine with dual oral combination therapy, which is basically standard of care at this point with close monitoring and management. However, pulmonary hypertension is still, by definition, an incurable disease. It's manageable, and management means making sure that the patients are not only on the appropriate therapy, but not overdoing it or not underdoing it. This requires close risk stratification, echocardiogram, right heart catheterization data if necessary, as well as management by an experienced clinician found mostly at a PH Center of Excellence. It really is important, I think, for patients to realize that their general cardiologists, their general pulmonologists, do an amazing job in being able to identify the disease. Most of the time, we're not the ones identifying the disease. We're the ones managing it. We get referrals because pulmonologists, cardiologists, and general practitioners understand how serious this disease is and being able to improve the awareness of the severity of this disease, especially since pulmonary hypertension is a relatively uncommon disease compared to things like diabetes and coronary disease, but just as deadly. I think is extremely important to be able to identify and send over to a fellowship trained pulmonary hypertension physician for management. This is particularly important in our underserved communities, which is why I think outreach is so important, especially in Native American reservations, across the landscape for patients in lower socioeconomic status who may not have access to not only diagnostic equipment, but treatment options too once they're diagnosed. We routinely care for patients who are not able to afford sometimes the expensive medications available that will treat their illness, requiring constant searches for sources of funding to provide for these patients to be able to manage their disease appropriately with the drugs that we know work for them. It is gratifying that pulmonary hypertension is now much more manageable than it was 20 years ago, but now it is very important to recognize the problem of access, the problem of specialty care, risk management, and treatment by Centers of Excellence because we need a comprehensive approach to management of disease. We cannot just treat the disease by itself because that will not help the patient. My name is Dr. Akshay Muralidhar, and I am 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/31778022

Episode 535 - Akshay Muralidhar, MD 08/26/2025

Raj Parikh, MD, MPH - phaware® interview 534 08/20/2025

Raj Parikh, MD, MPH - phaware® interview 534 Dr. Raj Parikh from Hartford Hospital discusses building on foundational pathways with treatment options for Pulmonary Arterial Hypertension (PAH) patients. He also emphasizes the value of clinical trials as well as the importance of a good doctor/patient relationship. This Special Edition Episode Sponsored by: My name's 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'd like to discuss building on foundational pathways, treatment options for pulmonary arterial hypertension patients. This is pretty exciting stuff. In the last year, we've had one of the latest agents to enter the pulmonary arterial hypertension therapy space, and that's the first and only combination pill. When we think about PAH and the pathophysiology of pulmonary arterial hypertension, we think about three foundational pathways. These three pathways basically result in too much restriction of our pulmonary blood vessels. What that does is it creates these three pathways as potential targets for therapy down the line. What we know about PAH historically is that these three pathways have created three different classes of therapeutic agents. We think about the nitric oxide pathway and the nitric oxide agents that then therefore intervene on that pathway and can treat PAH. We think about the endothelin pathway and then therefore the endothelin receptor agents that again, can intervene on that pathway. Then we think about the prostacyclin pathway. As the first and only combination pill, what it does is it takes two of these foundational pathways and develops it into one, combination, once-a-day, easy to use, easy to prescribe, cost-effective pill for patients. We just think about what that can not only do for patients in terms of compliance and adherence, but also decreasing their pill burden, making sure they're getting this dual therapy upfront, which is part of really our standard guidelines now for PAH treatment, which is using multiple pathways, multiple agents, not just one agent from one pathway for sort of standard of care. That's really what the foundational pathways and building on that and creating this treatment option for PAH, which is the first and only combination pill is really all about. A lot of what we do in pulmonary arterial hypertension, what we've learned is the more aggressive we are upfront, the better the patient's overall morbidity and mortality and prognosis will be on the back end. We've shifted away from a gradual, let's do one medication, let's assess your response. Let's do a second medication, let's assess your response. We've become a little bit more, what I would say aggressive upfront. Because what we've seen with that is that while we are aggressive, we're able to take a patient's, what we call risk score, risk stratification from something like high risk or intermediate risk and really bring them down to a lower risk score. When we do that, it's not just about creating a number of a risk stratification score of 12 to two. That two is really where the patient's quality of life improves. The patient's able to breathe better. The patient's able to do the things they want to be doing. The patient's able to live longer. The patient's able to stay out of the hospital, stay out of having to do routine invasive tests and things like that. Overall, the prognosis, the morbidity, the mortality changes as we have a lower risk stratification score. We really use our risk stratification tools. There's two or three out there. There's the European tool, there's the REVEAL score to really guide our therapy. What we've learned and what we've actually made standard of our clinical practice based on standard guidelines mentioned by the World Symposium on Pulmonary Hypertension, standard guidelines mentioned by the European risk stratification scores and European guidelines is to think about dual upfront therapy. That is basically taking a medication from one pathway, taking a medication from that second pathway and getting patients on two medications upfront right away for patients who have certain degree of risk. What that does is it improves their morbidity and mortality and prognosis by bringing their risk score down. So if we think about a medication like this, which is essentially saying, okay, well, we know standard practice is to be on two types of pathways, why not take those two types of pathways, spit it out into this one combination pill, the first and only ever combination pill in pulmonary arterial hypertension and make it easier for the patient. So now they're not taking up to 13 pills at three time intervals in a day, they're taking one pill at one interval once a day. This is cheaper for the patient. This is easier for these rare disease offices like PH clinics who have to order and get these medications approved through insurance. Now, they just have to get one medication approved instead of multiple, two or three or something like that. When you think about it from that angle and you think about rare disease in general, I think getting involved in clinical trials is almost like what you kind of have to do when you have, let's face it, limited options when it comes to pulmonary arterial hypertension therapy. I've been in this space managing and directing the PH Center at Hartford for four years. Prior to that, I've been as a fellow, really involved in learning about pulmonary hypertension for three years prior to that. In the last seven years, only one new medication, except for obviously this combination pill, has entered the PH space. There is limited options as a whole when it comes to pulmonary hypertension. Pulmonary hypertension is a rare disease. It's rare because it's overlooked sometimes. It's missed sometimes. It has a poor prognosis, and therefore there's not a lot of patients living for 15, 20 years with pulmonary arterial hypertension. That's just not the longevity of the disease. So when you're dealing with rare disease, when you're dealing with limited therapeutic options, getting involved with clinical trials is really important, especially when you're somebody who is a little bit more advanced, or you have a patient in your office who's a little bit more advanced than the common patient in PH who has a lot more deteriorated quality of life, a lot worse prognosis. Then, you're really looking at things outside of the box, outside of really these three foundational pathways, outside of what's really FDA approved for these patients and what else can you offer them? Can you get them involved in a brand new clinical trial for a medication that A, might have amazing outcomes, B, may have really neutral outcomes or C, god forbid, may have an increased signal for harm? But sometimes some of those risks really outweigh the benefits and sometimes the benefits really outweigh the risks for a patient who has poor prognosis in a rare disease space such as pulmonary arterial hypertension. When this combination pill, got FDA approved and was available in the market, what we did in our office, in our center was literally went through our list of patients and cold called them. We said, "You are already on the therapy that really this new medication contains." It contains one product from a phosphodiesterase or nitric oxide pathway, one product from the endothelin pathway, and it really takes it in and just spits it out into this one pill. "You are taking three pills once a day or you're taking 13 pills three times a day. That's really the combination that really would translate over to this new option." We called them up and we said, "You are welcome to make the transition.” It is, of course, rocking the boat. Now maybe you are fairly stable, maybe you are just freshly on these pills. Maybe you are on these pills for a long period of time, but you're not really stable and you could feel like you could get better. It's a balance between all those three types of subpopulations. Naturally speaking, the patients who are on only three pills and they're going from three to one and have been very stable and have been on that regimen for years, probably are a little bit more hesitant than, let's say the patient who's on 13 pills, three times a day and switching it over to just one pill once a day. Or if you take the patient who's on three pills, but it's for some reason for their insurance, that's a very expensive three pill regimen, and they're going to be able to really cut down their monthly costs in terms of pills and costs for the medications by switching over to this combination pill. So that's another type of patient, even though they're very stable, even though they've been on this regimen for several years, they really want to transition over. I would say that for the patients who were not treatment naive who have been on the different products that are contained into this combination pill, really anecdotally speaking, we have seen no sort of adverse or new developments or really curveballs in terms of making the transition. It's been pretty seamless for patients transitioning from being on the separate therapies into this really what we call loose dose therapies into this combination pill. My relationship with my patients is very important, and I think that focus is really because it's a rare disease space. When I'm going into my clinic day and that clinic day may have 20 patient visits for that day, 12 of them are follow-ups, patients I know. But eight of those 20 patients, almost half are brand new referrals, new patients I've never met before. They've never probably seen a pulmonary hypertension specialist before. They could be traveling from an hour, hour and a half, two hours away. Pulmonary hypertension, as we know, it's a rare disease. There's not a lot of providers who specialize in just pulmonary hypertension. There might be cardiologists who can dabble in pulmonary hypertension. There may be pulmonologists who dabble in pulmonary hypertension, but the space of pulmonary hypertension is limited in terms of how many providers are available nationwide, even worldwide. A lot of times patients who may have pulmonary hypertension, may have a concern that they may have pulmonary hypertension, may have already formally been diagnosed with pulmonary hypertension, may have to travel hours out of state, out of their area to come and visit a pulmonary hypertension specialist. With that visit comes a lot of pressure, comes a lot of pressure on the patient's end, comes a lot of pressure on the pulmonary hypertension specialist's end, comes a lot of pressure on the doctor who made the referral. That patient may have been for 30 years following with this cardiologist who is well renowned in their local town, who has managed all the cardiology issues for all of that patient's family members, their parents, their grandparents, and what have you. Now, that cardiologist is saying, "As seasoned as I am, as well as I know you, as well as I know your family, as well as I know this community, I'm sending you out of this state to a specialist in the city who is 30 years younger than I am and is not as experienced in the field in general as I am, but he or she is a pulmonary hypertension specialist." There's a lot that really comes with that. I think we sometimes don't put as much weight into all of that, but I think that's what is the pure beauty of really rare disease. That's what accompanies rare disease cases and rare disease patients and rare disease specialists. Now, you walk into their clinic room and they've traveled an hour and a half, they've been Googling about their disease state, rightfully so, doing their research. They've talked to the referring doctor who maybe is a long-term doctor of theirs, and they really have certain expectations from the provider. Now, I'm walking in and I want to make sure I can meet those expectations. I can really tell this patient, this is truly what I think is going on. These are the X, Y, or Z ways I think we can potentially make you better. And if those things don't work, this is my backup option. Or I'm walking in and saying, "Hey, you are very advanced, and if we don't do these two things, I don't think you can live this much longer." It's hard to say that to someone you've just met for two minutes who really is expecting to really make significant improvement by seeing you. It's a fine balance. I think sometimes being confident in your subspecialty disease, knowing what's available, knowing how to assess the patients, their prognosis, just having confidence in that process helps you maybe gain confidence from your patient. It's really hard. It's something that we all deal with in the rare disease space, is that how do we manage those expectations from the patient, from the referring doctor, and how do we invoke confidence in our patients? We want patients to trust us in this small field, in this rare disease field. We know what we're thinking about doing. We know what we want to do. We hope that it's going to be successful. If it's not, we know what our backup option will also look like too. When you stop and think about pulmonary hypertension patients, it's not just about the pulmonary hypertension pills that they're on. There's a couple pathways out there, like I've talked about. Those pathways yield certain types of medications. There's three or four maximal medications a PH patient can be on from a PH specific standpoint. But what about what other medications are they on? A lot of patients with pulmonary hypertension, they deal with heart failure. For that reason and that reason alone, these heart failure patients are on water pills. Sometimes they're on one water pill. Sometimes that water pill is dosed two to three times a day. Sometimes it's two pills three times a day. Now, a lot of times you're on two or three total water pills. So think about the pill burden from just the heart failure perspective. And the heart failure is simply a consequence of the pulmonary hypertension, but not treating the pulmonary hypertension itself. When we think about pill burden in PH patients, it's not just the PH pills, the three to five to 13 pills that they're taking three times a day. But now you add on the water pills, which are two to three times a day, two to three pills at every interval. Then with the water pills, you have electrolyte imbalances. So, now these patients are taking potassium supplements once or twice a day, magnesium supplements once or twice a day. Let alone if they have any other comorbidities such as diabetes or hypertension or hyperlipidemia. But let's just say just this pill burden alone is so overwhelming for these patients. So, to be able to take that pill burden and bring it down from 13 to one, from five to one, from three to one, in the large scheme of things, is a huge win in regards to patient adherence and patient compliance and cost-effectiveness, as well, for the patient. Thanks for listening everybody. A couple takeaways from my standpoint is obviously talk to your care team, talk to your provider before making any significant medication regimen changes. It's always important to be aware and ask about what active clinical trials may be going on, if that's something that you would be a good candidate for. I think that's important from just a disease perspective to know that these are the other options that are available to you out there. With pulmonary hypertension, this is a rare disease. I think the more we as a community can discuss amongst each other options that we have available to improve our quality of life, improve our prognosis, improve our medication adherence, these are all opportunities that we have to take advantage of. 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 /episode/index/show/phawarepodcast/id/35535790

Episode 534 - Raj Parikh, MD, MPH 08/19/2025

Robert Frantz, MD - phaware® interview 533 08/13/2025

Robert Frantz, MD - phaware® interview 533 Dr. Robert Frantz breaks down the key metrics behind risk stratification—functional class, six-minute walk distance, and brain natriuretic peptide levels—and explains how they shape treatment plans. He also explores the role of echocardiography, right heart catheterization, and cutting-edge therapies in improving patient outcomes. This Special Edition Episode Sponsored by: I'm Dr. Bob Frantz. I'm a cardiologist at the Mayo Clinic in Rochester, Minnesota, and Co-Director of the pulmonary hypertension clinic there. I have been working there on staff since 1990, so actually many decades of time of seeing patients with pulmonary arterial hypertension and seeing their therapies evolve. Today, we're going to talk a little bit about risk stratification and pulmonary arterial hypertension. I had the privilege to be a member of the at the Seventh World Symposium on Pulmonary Hypertension in Barcelona. This brought experts together from around the globe including patient representation in order to talk about the different risk stratification systems, how they can be utilized, and both discussing their use in clinical practice and also as tools and research protocols, as well. I would say that we had a very vigorous discussion at those meetings, because there are different risk stratification tools. Some people might say, "Well, if I have a really expert pulmonary hypertension provider, why do they need some risk calculator to plug in some numbers about me to say you're low risk, intermediate or high risk or whatever?" I'd say that's true to an extent, but there's a sense to which we all acknowledge that, number one, everybody seeing a PAH patient might not be a world expert. Number two, it is sort of objective and can be tracked over time and can avoid conscious or unconscious bias that can come into our thought process for whatever reason. Even things like, well, we like our patients, we want them to be doing well. It's hard to talk about maybe your prognosis is not as good as we would hope. Then, we might actually underestimate the severity of their disease because we're trying to be positive and optimistic. I feel like for me, who has been doing this for many years, I feel like, "Okay, I'm just going to objectify this set of information so that I'm keeping myself honest about where this person really is in terms of an objective risk calculator that might be a little different from how I'm viewing them today." The thing about risk calculators, they're used in many disease states in order to try to quantify prognosis with regard to risk of hospitalization or mortality. We know a couple of things. One, if you don't have very many of the components of the risk calculator, then it doesn't work very well. One thing we agreed on at the World Symposium is that there are various risk calculators, but key components are Functional Class I, II, III or IV. "Are you asymptomatic or are you short of breath at rest?" Functional Class III would be if you go up a flight of stairs you get breathless. That's one metric. So, that is one component because the more advanced your Functional Class, the more concerned we should be about you. The other thing is six-minute walk distance, like how far can you walk in six minutes? That is quite closely related to prognosis. That's why it's important for patients to be doing those six-minute walks and trying during that time to walk about as far as they think they can in that six minutes, even if they have to rest or stop a couple of times, because it's a reproducible way of assessing whether they're getting better or worse or about the same. The third component is brain natriuretic peptide or N-terminal pro-brain natriuretic peptide, which is a mouthful, but it's basically a protein made by the heart that is released to try to help our kidneys dump fluid and salt, so kind of what we call a counter-regulatory hormone, that if the pressure is going up inside the heart, in the right atrium and things, we release more of this to help the kidneys get rid of fluid and salt. We use it as a prognostic marker. You can, as a patient, know what your BNP level is next week and you could have it checked again in three or six months and might follow that over time with the idea that if that value is rising, that might be of some concern. If it's dropping, that might be reassuring. The thing about that particular metric is that there's two assays. One is called BNP, just brain natriuretic peptide, and the other is N-terminal pro-brain natriuretic peptide. Different hospitals and systems might use the different assays. It's important to know which one is being done, because otherwise a person could be rather concerned that the level's changing dramatically. It's just actually a different assay depending where you had it done. The NT-proBNP circulates at levels that are four to eight times the BNP, so they're very different metrics. I think the bottom line is the risk calculators that include a variety of things that include the REVEAL risk calculators 2.0 and what we call 2.0 Light and the European calculators, which are things like COMPERA and COMPERA 2.0 have some differences, but all of them include functional class, six-minute walk distance and brain natriuretic peptide levels, and may include other things that are things like in for REVEAL 2.0 is heart rate where if your heart rate's high and your blood pressure is low, that's concerning. So high heart rate over 96 beats per minute or low blood pressure sort of in a way that would be of concern also would go into that risk calculator. In the REVEAL 2.0, if you have renal impairment, so that when you see these calculations being done, you can think about what's in the calculator. When we think about that risk calculation, baseline when people are first diagnosed, are you low risk, intermediate risk or high risk? Almost everybody, even if they're both low and intermediate risk are getting an endothelin receptor antagonist and a phosphodiesterase 5 inhibitor, what we call dual therapy. If they're high risk, they may be getting IV or subcutaneous prostanoids plus an endothelin blocker plus a phosphodiesterase 5 inhibitor, what we call upfront triple therapy. The precision of that risk estimate just has to get your provider in the ballpark that they're going to provide you at least dual therapy or maybe triple therapy. The goal of the risk calculator is to try to get patients to low risk if possible, a good six-minute walk distance, a good functional class, not being out of breath going up a flight of stairs, having a natriuretic peptide level that's normal or low as opposed to high and rising. These risk calculators are especially useful when patients come back, because then they're already on some treatment, and is that treatment actually working or not? Patients and family members might get frightened that they're in a high risk or intermediate risk category, but need to recognize that the important thing in a way is when they come back in three to six months, is that risk lower now, are the therapy's working? So, redoing that risk calculation and saying, "Oh, the six-minute walk distance is a hundred meters farther and your brain natriuretic peptide level is significantly lower, and now you're not short of breath on stairs. We're feeling like you're now in a low risk category. Let's stay with these two drugs we're using." Or, "Actually things aren't quite where we want them to be." The beauty of the risk calculator, in a way, is its objectivity. Sometimes the patient will say, "Doc, I don't know you that well. Do I trust you, you're really expert about this? You really want me to add another drug? Is that just because you want to be aggressive or do I really need it?" Having an independent risk calculation that says, "Yes, actually you're still at intermediate risk for a bad outcome," can sometimes empower patients to understand that it's just not me as a provider saying I think they should do this or that. Any group of experts would say, "This person is still at intermediate risk. They would benefit from additional therapy and it may be worth putting up with some side effects to reduce the risk." The other way we use these risk calculators sometimes can be in clinical trials as a secondary outcome measure, that is, is your risk calculated score improving on average with therapy or not? The other way we can use them is that if we have a set of patients who went into a randomized clinical trial of a PH therapy, we can characterize those patients by low, intermediate or high risk. Then, at the end of the trial can look and see which patients benefited the most. Then, when I'm seeing a patient in a clinic and I'm saying, "Should I apply this drug from this clinical trial in this clinical situation? How does my patient compare to the patients who did or didn't respond to the therapy?" An example of that would be that analysis in the GRIPHON Trial, which is the study of selexipag, which is an oral IP receptor agonist as therapy for pulmonary arterial hypertension. On average, there was benefit in the patients who received the drug, but the patients who are actually at highest risk going in maybe benefited somewhat less. Maybe those patients actually would've been better off just going on to an IV or subcutaneous continuous prostanoid therapy as an even more aggressive therapy. We might say people at lower to intermediate risk, adding the selexipag could be very useful. If they're at high risk, then probably they'd be better off to go with even a more potent therapy. That kind of information can help us understand how to personalize our treatment for our patients based on the risk category. General consensus was that you should be reassessed clinically and with regard to risk at three months after making a treatment decision, because most of the therapies that we give are going to be effective or not as effective as we like within that timeframe. Then, at that three month point, there'll be a reassessment, and then maybe a slightly different direction. Then, another three months later should be assessed again, and continue that every three month kind of recheck until a person is at low risk or on all the therapies we have available. If they're stable and on the therapy we think is optimal, then we might back off to every six months. I think that the issue of reimbursement and coverage of medications is one that we all deal with on a regular basis. I would say that the clinical decision to add another therapy generally isn't going to be second guessed based on a person's risk categories or something like that. If the clinician thinks another drug is appropriate, then, usually, that will be accepted. It may be that there could be some pushback where if we say they're at high risk, they need IV or sub-Q continuous prostanoid and they're not yet on an endothelin receptor blocker, which is an easier oral agent that maybe the insurance companies say, "Well, you should be adding that, and they have to fail that before they go to the continuous infusion." We might say, "They're too sick to do that now. We need to move to this other therapy now and can talk later about whether to add or subtract or something later." There can sometimes be that where if you're sort of leapfrogging ahead because they are not on aggressive enough therapy, there could be some pushback that you haven't tried something simpler. You have to say, "Look, in my judgment, we can't go simpler. We need to go with a more aggressive program." So, that can sometimes be an issue. This World Symposium tends to meet about every five years. It's only one forum for our discussions about optimal strategies. There are many other forums that can include consensus documents that different scientific groups put together like the pulmonary or the cardiology societies and position papers that people might write, or just best evidence-based recommendations from a set of experts that might get published. So, there can certainly be updates to these things. I think that one component of the World Symposium Review on Risk Calculation included a couple of things for saying directions we need to go with this. One includes that there's not very much echocardiographic guidance in the risk calculators, partly because there wasn't very much echocardiographic information in the registries that resulted in development of these calculators. So, if you don't have that information in there, it's hard to incorporate it. One of the recommendations was that in addition to using these risk scores, we should also be keeping track of echocardiography in terms of how the right side of the heart is behaving, how big are the chambers, how impaired is the function of right ventricle, how much is the tricuspid valve on the right side of the heart leaking, and use that as supplemental information to our risk score. You might have somebody who's young and they've otherwise been pretty healthy, and they still can walk quite far on a six-minute walk and maybe their BNP level isn't very high, but when you look at their echo, the right ventricle is quite severely impaired. That might be something where you say, "Well, I don't think the risk calculation is actually taking to account what's happening with this patient's right ventricle as fully as I would like. So, we're going to incorporate that right heart ventricular function information, into our decision-making and that the onus is on the community to continue to try to develop better and more widespread utilization and metrics for what the right heart is doing in terms of performance." That's one thing that the field is going to continue to work on. It's like, "What on the echo should I be looking at that tells me that they should have more therapy?" The other thing has to do with hemodynamics and right heart catheterization. From the echo, we get estimates of pressure. We might get some estimate of the flow of the heart and cardiac index, but it varies in accuracy across centers and patients. There is the understanding that in situations where we're not sure which way to go, where sort of some low and some intermediate and maybe some high-risk features, that repeating a right heart catheterization in order to get very objective, accurate information about the cardiac output and the right atrial pressure and the cardiac index and things can be useful. Especially, as we start to have developed drugs coming along like sotatercept or Winrevair, which is this anti-proliferative that's scavenging growth factors in the blood, given as an injection every three weeks, that may lower the pulmonary pressure and lower the resistance, that repeating right heart catheterization and seeing how much better are things in that objective way might help us, especially if we're trying to make decisions about backing off on one of the other therapies. We know our prostanoids, the infusions, the inhaled drugs, the oral therapies, that prostanoid class of drug has the greatest side effect burden, and is maybe most hard for patients in terms of quality of life and having to deal with that. If some of our anti-proliferative therapies are successful enough, maybe we can reduce the burden of our therapies by reducing that prostanoid or maybe in some situations even taking it away. But if you're going to be doing that, you need to be really sure where things stand and maybe a risk calculator, and how far people can walk and their functional class isn't quite enough to be sure about that. Especially now, we're talking about backing off on other therapies for improving quality of life and burden of the therapies, repeating a right heart catheterization to know where we really are could be very useful. Another thing I'd say about risk calculators is number one, they can be incorporated into electronic medical records. So then, that is living in that electronic record and can be flow charted like, "Okay, this patient's REVEAL risk score was 9 three months ago and now it's 7." I can see that difference and I can track it. The other thing is that there are apps. If a person just Googles, “pulmonary hypertension risk calculator,” it can take you to a website that has all the different risk calculators. A patient could do that themselves if they wanted to, if they have that information. So it could be sometimes somewhat empowering if they choose to do so. Go there and say, "Hey, what's my REVEAL 2.0 Light risk score after this last visit," if my provider didn't tell me or didn't calculate it? It always needs to be put in the context of the patient. I think that was another message from our debates at the World Symposium about this, is that this is one modality to assess risk. It has to be put in the context of the echo, the human dynamics, patient goals, where we're talking about patient-centric medicine. So we could say, "Oh, you're at intermediate risk, we should add a prostanoid." Then, the patient has to do some thinking about that, "Am I willing to take on that side effect burden to try to reduce these risk characteristics, or will it help me feel enough better that it's worth the side effect burden?" We can get caught up in this objectification of risk and things, but realize this is a person sitting in front of us with different goals, and maybe we're not engaged in a way where we really understand what they're looking for. If we're mono-focused on reducing risk and adding more drugs, maybe we're not really meeting the patient where they are in terms of their journey. I always like what Rino Aldrighetti, the former head of PHA used to say, "Every patient has the opportunity and the ability to fight this disease as much or as little as they choose to do." We have to accept that, that we might be all in, "Do this, do this, do this." Is that really where our patient is? So, I think that's the other message, taking it back and being patient-centric, "Here's the information. Let's talk, what are our joint goals here?" Thanks so much for listening. My name is Dr. Bob Frantz, and I'm aware 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 #RiskStratification /episode/index/show/phawarepodcast/id/35847280

Episode 533 - Robert Frantz, MD 08/12/2025

Jean M Elwing, MD - phaware® interview 532 08/06/2025

Jean M Elwing, MD - phaware® interview 532 ICU & You: What Happens When Pulmonary Hypertension Turns Critical? Pulmonary hypertension is already a complex condition, but what happens when it becomes life-threatening? Dr. Jean Elwing breaks down what patients and families can expect when someone with PH ends up in the ICU. My name is Dr. Jean Elwing, and I'm a professor of medicine, and I'm the director of the Pulmonary Hypertension Program at the University of Cincinnati, and 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. So today I want to talk to you about how we approach a patient with pulmonary hypertension that's in a critical situation in the intensive care unit and how we manage the medications that are very helpful to you as an outpatient, but how we do assess and how we use those medications inpatient when people are very sick. So there's multiple situations that can bring a patient into the ICU. They could rapidly worsen in terms of their right heart function. If they would have an arrhythmia, irregular heartbeat, or a blood clot or something would change dramatically with their medications, or they could gradually be worsening over time, or they could be a new patient that had never been diagnosed before. Each one of those scenarios we treat a little bit differently, but the thing we can't forget is the origin of the problem is the elevated pulmonary pressures. So once we figure out why they're elevated and why that individual has right heart stress and strain and going into right heart failure, then we can intervene. In patients who have progressive pulmonary arterial hypertension or patients who are newly diagnosed, the main focus should be addressing the pulmonary vascular changes and trying to unload or relieve the stress of the right heart. And we do that through our pulmonary vasodilators. Each individual patient will be assessed based on their specific needs, but in general, we try our best to initiate medications that relieve that pulmonary vascular resistance as soon as we can. Oftentimes we start with things we can get to the patient very quickly like an inhaled therapy such as nitric oxide or inhaled epiprostenol. And then we take a few minutes, we look at our situation, we look at that individual patient and then decide is this a person that should be given infusion therapy, continuous IV medications to help reduce that stress on the right heart? And in most circumstances, that is what we do when patients are critically ill with pulmonary arterial hypertension and right heart failure. We also ask the other members of our team to help us make sure we address all the issues that could be contributing and anything else that could be worsening the situation like low oxygen. We would give you oxygen in a way that would raise the levels to a point where it no longer is causing stress on the right heart. And sometimes that's through a nasal cannula, sometimes it's through a non-invasive machine like a CPAP, and sometimes it requires patients to have a tube in their throat to be intubated and put on mechanical ventilation. So we have to figure out what need that individual patient has and then address it the best way we know how to take care of them. The other thing we'd look at is how much fluid they have in their body. Is it a low fluid state or a high fluid state? Most of the time when patients are in right heart failure, they have extra fluid and we try our best not to give additional fluid and then gradually try to help the person get rid of extra fluid through medicines called diuretics. We also have members of the team that could help with mechanical support. That is in our most severe situations, we look to people that could help us offload the work of the right heart by a machine, and that's usually ECMO. So it's a circuit that helps circulate blood, give oxygen, and get blood to the right places in the body to give the body a chance to heal. Now, that's not an option for everyone, but in rare circumstances when the medications are working but not fast enough, we have to have a bridge to give the body enough time to heal and hopefully recover from that serious situation. No one part of this equation will get the person better. It has to be a multiple intervention all at the same time working together as a team to get the body to be able to get back to the point where you can breathe independently without extra oxygen, without a machine, and get the medications up to a level where your body can heal enough to be able to go back home or go to a place where you'd have additional time for rehab. So it is a very complicated situation. We try to avoid patients getting sick to the point where they need the ICU, but this is why we have an ICU. So we can rescue people in circumstances that are very dire. So of course we never want a patient to be faced with a situation where they're critically ill, but we always want you to be prepared. This is something that we talk to our patients about oftentimes when they're first diagnosed. Then as you're on medications that are complicated and sometimes infusion therapies for years, we may not revisit that, but we want to remind everyone who's involved, the caretaker, the patient, the support individuals that we want to be ready. So be prepared in terms of having medications and your go-pack ready if you would have a situation where you'd need to go to the hospital quickly. And if you're away from your home or you're in a remote place where there's not experts in pulmonary hypertension, then make sure that doctor that sees you and the person that does the intake when you get to the emergency room knows you're special, you have special needs, and you can't be treated like everyone else. You have to be treated in a way that takes care of the underlying problem, maybe an injury, maybe appendicitis, but in the context of your pulmonary hypertension, we manage things very differently. We change how we treat you with different medications. We also change how much fluid we might give you. So those are really important things, I think, to remember and to have on your list to be ready for anything and everything because that's how life goes. The minute you think things are quiet, something comes up where you might need some extra attention. We see each patient as an individual. Pulmonary hypertension has so many different faces and so many different levels of severity. So usually the first thing that happens when you come to the hospital and you're sick and you're seen in the emergency room, the ER staff is very aware of the complexities of pulmonary hypertension and they oftentimes call a consult to the pulmonary hypertension team, which may be a cardiologist in one center or a pulmonary in another center, and they get them involved and they look how the patient is doing. If you're the individual patient being seen, they'll assess how your heart's doing with an echocardiogram. They may do labs to look how the kidneys are functioning and labs to look at stress and strain on the heart with an NT-proBNP or a BNP. They'll look at blood pressure, heart rate, and urine output and try to figure out what is exactly happening with the level of risk you're at for having worsening symptoms or for worsening right heart failure. And then we'll decide are we having a problem with medication? Was there an interruption in medication? Do we need to go up on medication or do we have to start something totally different? So really depends on what's happening.= And then of course we go through all the things that could trigger the pulmonary hypertension to be less well-controlled, meaning we think about thyroid disease, we think about infection, we think about medication interruption or anything that could set off the fine balance that you as a patient are in on a routine basis. And then once you're admitted to the hospital, you would be admitted to the location that can take care of patients with pulmonary arterial hypertension or pulmonary hypertension of other sorts. In that location we hope to be able to deliver care that's very sensitive to your needs and take that into account when we choose different therapies that we give you for whatever is triggering the episode of worsening pulmonary hypertension. One very common thing that triggers pulmonary hypertension worsening is irregular heartbeats, fast heartbeats, or what we call arrhythmias. In that circumstance, we would give you medicine oftentimes to help control that heart rhythm, but we choose specific ones that fit the needs of pulmonary hypertension patients. We would interact with our cardiology colleagues that focus on arrhythmias so we can do our best to control that, because controlling that arrhythmia many times will help you to be able to recover from that worsening event. Another thing that frequently gets patients in trouble with pulmonary hypertension is infection, and so we're very mindful of that. We try to treat infection early and treat it in a way that you tolerate, meaning not too much fluid and be very cautious about the oxygen changes that may occur in circumstances like pneumonias. So it's really complicated when you get sick and need to come to the hospital, but it really takes a team approach and to really hone in on the cause of the issue and make sure we support the pulmonary hypertension in the meantime. Of course, we always want the happy ending to every hospitalization, but sometimes things don't go that way. And sometimes there's things that are not recoverable easily with our routine medications. And as I mentioned, sometimes we look to a mechanical support with ECMO to support patients, but not everybody's a candidate for that because of various reasons. And so one thing we always have in the back of our mind is could you be a transplant candidate if you're really sick with pulmonary arterial hypertension and right heart failure in the ICU? And if so, that's a conversation we would have with you. The things we pay attention to very carefully when patients are sick in the ICU and we're thinking about transplant are a lot about your history and what might make you a optimal transplant candidate or some things may limit that option for patients. And so we look at things like social support, history of other medical illness, age, also weight plays a role, and if you're even interested in that. And if you are and you're the right type of person for a transplant evaluation, we would contact our transplant team and colleagues and see if this is the right time to complete that evaluation. Sometimes they would like us to continue to support, try to get you better before you are seen in the transplant center. And sometimes they want to start the evaluation right away. Some centers have a transplant team right there with them. In my case, I do not. I work with outside facilities for transfer, so we would work with another hospital system and then it would be a transfer to that location. So it really depends where you are, what your interests are, and what your history is to determine if transplant might be the next best step. When pulmonary hypertension patients develop a severe illness and they require urgent evaluation, we require a higher level of care to be delivered to the patient because of the complexities of pulmonary hypertension, the right heart function, and the medications that patients are on with pulmonary hypertension. So this is a circumstance where we have to be very mindful. We have to make sure all the team members are aware of the history of pulmonary hypertension, the specific medications the patient is on, because any piece of the puzzle that's left out will result in the patient with pulmonary hypertension not doing as well as we would like them to. So it is a very complicated situation. We want to take it very seriously. We want patients to be ready for these situations, and we want to work together with a team, including the ICU physicians, the ER physicians, the surgeons if we need them, the cardiologists and the pulmonologists to get the best outcome. 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 /episode/index/show/phawarepodcast/id/36413870

Episode 532 - Jean M Elwing, MD 08/05/2025

John Granton, MD - phaware® interview 531 07/30/2025

John Granton, MD - phaware® interview 531 Dr. John Granton, a critical care and transplant physician at Toronto General Hospital, shares his journey in pulmonary hypertension and lung transplantation, detailing the groundbreaking advancements in transplant technology. He discusses the evolution of lung preservation methods, the challenges of chronic rejection, and the hope for longer-lasting transplants. With a passion for improving patient outcomes, Dr. Granton envisions a future where transplant becomes obsolete—replaced by treatments that cure underlying diseases. My name is John Granton. I'm in Toronto. That's where I was born, just north of the city. I trained mainly in Canada, trained in London, Ontario and then went to McMaster and then University of Toronto and then University of British Columbia for a while and came back. I've been on staff there for about 30 years now at the Toronto General Hospital, primarily. I work as a critical care doc looking after sick patients who come in ill or after major surgery like transplant. I've also worked in the transplant space for many years as a transplant physician, but more commonly now as a critical care doc, looking after people after transplant. We started a pulmonary hypertension program in 1997. At the time, the head of transplant, Stephen Kestin, looked to me and I'd just come on staff. The paper on Flolan had just come out and he said, "We need somebody to do this." He said, "You like hemodynamics and stuff and you're a critical care doc. Why don't you do this?" I said, "Okay." I got some money together. We hired a nurse part-time, put a sign on the lawn and we've grown. We're a big program. Because of the resource, we serve a lot of different communities. We offer the range of critical care and transplant services in addition to pulmonary hypertension services as a major referral center. We also provide medical treatments, diagnostics, chronic thromboembolic pulmonary hypertension management, so major surgery. I’m really here today to talk about the transplant aspect. Our program in Toronto is a big program. We transplant over 200 patients each year, so it makes us pretty much the largest program worldwide and a highly innovative program ,as well, doing a lot of really cool things, which ultimately will benefit patients by providing them with access to more lungs, so they have the opportunity to benefit from transplant, and also looking towards better outcomes for transplant. One of the major things we're doing is looking at the role of when we get a lung from somebody who's died or a set of lungs from somebody who's died, we put them on this machine, which actually profuses it. We run a solution through it and we support it, kind of in an animated state, which allows us to check out the lung to make sure the lung's okay, functioning well, make sure there's no pneumonia. We can look into the lung with a small scope. We can take x-rays, CT scans. Our group's now modifying the lung, so you can actually treat the lung to make it better. You can make it perhaps more acceptable for the person, so they don't have to use as much immunosuppressants to suppress their immune system so they don't get infections and stuff, so they can tolerate the new lungs with their immune system better. Ultimately that will lead to better outcomes. The major problem with transplant right now is that once you're committed to transplant, those lungs are yours. We know that in addition to the trouble with the drugs, those lungs will eventually fail because the body will continue to try to reject them. That's been the major limitation to transplant. Hopefully, with this kind of technology and availability and understanding of the biology and how things work, we're going to be able to manipulate those lungs so that they've got a much longer shelf life, if you will, and carry the patients through for a lot longer than it currently is. Usually, when we identify somebody, a set of lungs for a person, we call the person and we also call another person often as a backup, just in case something's going on. You can only have the lungs outside of a person's body for a period of time before it starts to deteriorate. Having it on the system actually allows them to be animated for a longer period of time, so you can kind of coordinate things a little bit. Previously ,people had to live close to the hospital. They couldn't be more than a couple of hours drive, because they had to be available to go to the operating room real quick and you had to make decisions fairly quickly. Now, it puts us in the position where we can bring people in, they can drive from home a few hours away. When they're in the hospital, they kind of go in a waiting room and they sit there and hope that the lungs are going to be okay. Often, it's a dry run because the lungs don't turn out okay, because there's something wrong with them or they deteriorate. When you start to look at them, they're not performing well, so you don't want to put it in the person. Even though that's discouraging for the person, it otherwise avoids them getting a set of lungs which may not have served them well. I think it also increases confidence that the lungs you're putting in are probably going to be good and you've improved them and they're looking better, and so you're much more confident in transplanting them into the person who's waiting. In the old days, you didn't have that confidence and so you turned away a lot of lungs that might've otherwise been pretty good, but also you may have put in some lungs which you wish you hadn't because things start to turn sour fairly quickly. Once they're in somebody, you can't look back. Transplant used to be kind of an experimental therapy. Now, it's an established therapy. Treatments have improved and medications, particularly cyclosporine allowed transplant to occur successfully. Previously most grafts, kidneys, livers, lungs would fail very quickly. The advent of cyclosporine really allowed transplant to occur. The problem with lungs is of all the organs, they tend to do the worst long-term. The reason for that is this ongoing rejection that can damage the lungs and cause them to not work properly and patients often have to go back on oxygen and other things like that and they start to feel short of breath and their quality of life, frankly, starts to deteriorate. If you look at things like survival, the average survival in many programs is about seven, maybe eight years for pulmonary hypertension. If you get through the initial phase, pulmonary hypertension patients who are transplanted do better than other reasons for being transplanted like COPD or interstitial lung disease, IPF. They still succumb eventually from this problem and we're trying to manipulate that, but we haven't found the secret recipe yet to prevent that from happening. We're hoping that by conditioning the lungs early on, allowing better tolerance of the lungs will prevent that lungs standing kind of erosion of the lungs because of ongoing rejection or attempts at the body to try to get rid of those lungs, which can damage them. We haven't found that yet, and it really is the Achilles heel of lung transplantation, this chronic rejection. We do occasionally have to retransplant somebody. We never really go in saying, if these lungs don't work out, you're going to get retransplanted, because we don't know if that person would be eligible for another of lungs. Generally, you go into transplant with the understanding that's probably your shot at it, with those sets of lungs. Occasionally, we can re-transplant people, but that's usually the exception as opposed to the rule. After transplant, because of the medications, you accumulate a lot of complications and you're also a bit older and you're also subject to the same kind of conditions that everybody else gets. Heart disease, kidney disease, liver disease, other things. Whereas you might've been a good transplant candidate at the time you got your first set of lungs, you may not be a good transplant candidate by the time you need a second set of lungs. So, you really have to hope that those lungs carry you through. Even though we talk about the average survival being seven and a half, seven, eight years after transplant, but some people don't do well early on, but many patients do better than that. I still have some of my patients, I still run into the hallways 20 years after transplant. That's amazing. It's still too short. If you're a young person, 10 years is still a short period of time, so we'd like to be able to offer everybody a normal lifespan and look forward to that one day. Secretly, I hope transplant goes out of business. That'd be fantastic, so that you could actually treat the underlying conditions and people would never need a transplant again. That is the ultimate. Transplant is really a failure of medical therapies to treat the underlying condition, whether it be heart disease, kidney disease, liver disease, whatever. Some of it is self-inflicted. We do recognize addictions that can cause lung disease and liver disease. Not so true for pulmonary arterial hypertension or people have pulmonary hypertension from other causes. Apart from those instances, but also treat people who have those addictions better, but also treat people with pulmonary arterial hypertension in particular with novel medications which might reverse the disease and at the very least prevent further progression of the disease so that people won't need transplant. That's kind of the holy grail is to get to that point. I don't think any of us would lose sleep if we never had to send our patients for transplant. When you actually start talking about time though, when your life expectancy with the condition you have is worse than the life expectancy after transplant, and that's kind of the trade-off. You have to decide, okay, if average survival after transplant is seven and a half years, what's my average survival right now? If it's less than seven and a half years, then that's probably you're going to want to start thinking about transplant. Some conditions and the level of severity means that you're much higher risk of not surviving the next year or two. So, transplant becomes much more in the moment the conversation. It's a tough conversation because it's hard talking about the future and what that looks like and accepting your mortality and the timing of that. It's an upsetting conversation to have with people and it's upsetting for them and traumatic for them and their family to have those conversations. They thought about it. There's another conversation though that I often find is a bit easier is that, “What's your quality of life like right now?” If we can't make that better through medication, we tried everything, at what point does your quality of life get so impaired and you're so unhappy with the way you're living and the things you can't do that you would be willing to risk your current situation for something better like transplant. I think having that quality of life conversation is a little easier sometimes than having the death conversation, because ultimately we accept that we're all going to die one day, but we hope we live well up until that point. That's the way I frame the conversation. It's much more around, “Let's talk about ways to improve your quality of life.” Transplant is a way of doing that. It's hard to generalize, but I get a kick out of seeing patients after a successful transplant. I don't even recognize some of my patients ,because you saw them when they couldn't walk and they were carrying oxygen. I remember people with cystic fibrosis, they couldn't get along and they were coughing, a terrible quality of life. People with pulmonary hypertension really having to stop and pause and do things when you catch them walking from the waiting room or down the hall or wherever. Then, they're walking briskly to have their lung function done. Or I seem them out in the street somewhere and you just don't recognize them. They tap me on the shoulders. It's fantastic. As I said, some of the patients I've known for 10, now 20 years, you run into them and it's amazing. I get a real kick out of that. To me, it's been transformative. Even those patients who I see who aren't doing well and maybe they're starting to get some rejection or their lung function's deteriorating, I ask them, “Was it worth it? Would you do it again?” They say, “Yeah, I would do it again. The years that I had were amazing. I was able to do things I could never do. I really got to enjoy my family. I traveled, I started riding, walking, hiking,” whatever they enjoy doing. That's really what it's all about, to get them back to that point where they want to be and live life. It's fun when they're able to do that. My name is John Granton 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 #transplant /episode/index/show/phawarepodcast/id/35845670

Episode 531 - John Granton, MD 07/29/2025

First 5 Minutes® - phaware® interview 530 07/23/2025

First 5 Minutes® - phaware® interview 530 In this episode, Drs. Victor Test, Deborah Levine and Rodolfo Estrada discuss CHEST’s program, which helps medical professionals build the skills that lead to a positive relationship with patients from the get-go. The goal is to improve patient care, shorten time to diagnosis for complex or rare diseases like pulmonary hypertension, and increase patient compliance and buy-in to their treatment plan. Victor Test, MD, FCCP: I'm Dr. Victor Test, Chief of Pulmonary Medicine and Critical Care at Texas Tech University in Lubbock, Texas and Director of the Pulmonary Vascular program. Deborah Levine, MS, MD, FCCP: Hi, I am Debbie Levine. I'm a lung transplant and PH doctor and I'm working at Stanford University. Rodolfo Estrada, MD, FCCP: Hi, I am Rodolfo Estrada. I'm a UT Health San Antonio pulmonologist and working in pulmonary hypertension, as well. Today, we want to share a little bit about the First 5 Minutes initiative from CHEST, which talks about how do we approach patients in the first five minutes to gather the most amount of information, create trust, and build up empathy to better care for patients. Victor Test, MD, FCCP: The First 5 Minutes program was developed in response to our recognition at CHEST about the difficulty that had developed during the period of the COVID pandemic with trust between patients and healthcare professionals, and particularly physicians. As you know, during that time we were all particularly challenged because of lots of information in the media and doubt and fear with patients. The difficulties we faced in ICU care of critically ill patients with isolation and the difficulty that families had with that. So in response to that, we developed something called The Listening Tour where in five different cities of the US, including San Antonio and San Francisco and Atlanta and Chicago, we went out and we recruited patients and we spoke to them about the challenges they had faced with their chronic lung diseases. They ranged from asthma to COPD to pulmonary fibrosis to pulmonary hypertension, and how their patient journey was impacted by their interactions. What we learned was that there was a significant breakdown in trust. As a physician, usually I go into a room assuming that I have trust. What we really realized is that physicians have to build that trust and develop that trust. It isn't just given to us as an anointment because we're a physician and we're there to try to help. So we developed at CHEST this program called the First 5 Minutes. The concept of it is that physicians and healthcare providers need to develop a rapid rapport and understanding of the patient and develop this trust with active listening, empathetic listening and direct feedback with emotional support while incorporating the patient into the decision-making process. Deborah Levine, MS, MD, FCCP: I think really what the First 5 Minutes is an approach to how we as physicians can interact with our patients when we either don't know them or do know them, to kind of build a bridge of trust but also learn to respect each other in terms of being able to understand the best ways to communicate and also understand. I think patient understanding is a big part of it. Rodolfo Estrada, MD, FCCP: The beautiful thing about the First 5 Minutes is that you can use it for new patients and follow up patients because it caters to whatever the patient thinks is most important for them for that visit. Sometimes, we pre-chart those patients and have an idea of what we want to talk about, but the patient has new findings and new developments happening. If you take those first five minutes and you take a moment to really elicit that out, most of the times the patient will bring it up but won't be the first thing that they bring up. One of the tools that the First 5 Minute initiative has is that you ask, “What else? “Then you ask again, “What else?” Then you ask again, “What else?” Maybe by the third “What else,” the real conversation comes on, and then you can develop the rest of the time talking about it and still do your clinical part that you have to do, but in alignment to what's important for the patient for that specific visit. If it's emergent, they'll bring it up quicker than the other ones, but otherwise I think they'll still be able to bring it up. Victor Test, MD, FCCP: What we're trying to do is to push this program forward so that we spread it out to physicians at all levels of training as well as post-training, so that it permeates throughout the US healthcare system. We'd really like for it to eventually be part of every training program and post-training program so that our physicians can breach that divide between patients and physicians. It really doesn't have to be physicians, it could be physicians assistants, nurse practitioners, nursing, medical assistants. Anyone can be taught these skills. Sometimes, there's a concern by people when they hear about this, the say, “Well, that's going to take a lot more time.” In fact, studies show that empathetic listening and patient-centered interviews actually take less time and they make the healthcare more efficient. It actually has a win-win solution for most physicians if they're able to use these skills and it helps the patient and develops trust, we believe. This tool set and this educational program can make a big difference for our pulmonary critical care physicians. Ultimately, the goal here is to improve patient care and to incorporate them into decision making. We believe and we hope that that would decrease time to diagnosis for difficult to diagnose or more rare disorders. Certainly, we wanted to improve healthcare for patients so that we can help identify the obstacles that they face, and improve their compliance and their buy-in to whatever program we develop for them for their care. It aligns the patient and the physician so that they can each achieve the goals that the patient and the physician have, and put them in parallel rather than disparate pathways. Deborah Levine, MS, MD, FCCP: The idea that we as a community, I'm talking all physicians whether it be PH or anything else, we are limited often in time. If you are in a busy pulmonary clinic where you're seeing 30 patients in the morning and 30 patients in the afternoon, you may have some type of preconceived notions or preconceived ideas about what this patient has. So leading that patient, you may be leading him or her to say what you believe they have. This way, I think it is more efficient, because you can then say, "Hey, listen to the story.” Take the five minutes and listen to the story. It may not be asthma and it may not be COPD, which is what many of our patients are diagnosed with instead of whatever they have. I think this can help that bridge to understanding what the patient has, but also it can do it in a way that also kills two birds with one stone. You maybe get a more efficient trajectory in terms of getting a diagnosis, but also you make them feel so much more comfortable. Rodolfo Estrada, MD, FCCP: I think that's something that's important within the rare disease space with PH being one of them, is that, as humans, we're prediction machines. When we see someone with shortness of breath, we're going to go and think about what's the most likely diagnosis from what we've seen in the past. In the rare disease space, that becomes challenging, because then we have to pause. Having that pause initially when you're first going to see the patient and checking if your biases, if your assumptions, are correct. That can be taught and doesn't need a lot of time. So a nurse that sees a patient before the provider goes into the room can have that same approach of pausing, and making sure that what we're seeing and what the patient is saying are congruent things. Victor Test, MD, FCCP: One of the things that has been observed in medical interviews is that patients often are interrupted quite frequently by healthcare providers to try to facilitate their story. When in fact, when patients are left to tell their own story they often give a more complete and thorough story than we as healthcare providers would like to ask. So the PEARLS is an acronym to remind us of important points in interacting with the patient. They range from personal to support, and empathy, acknowledgement. When you use those in a patient interview, you don't have to use them all in every interview. In fact, if you did, you probably would defeat the purpose of them. But to use those different points to help you to connect with the patient and help each other understand the healthcare that they're receiving is actually a team between them, their family and the healthcare providers that they're seeing. Deborah Levine, MS, MD, FCCP: I learn a lot more about patients, their families, and their life. There's no question that that comes organically. Empathy isn't something you have to think about, it just happens, because if you hear these patient stories, if you hear their families talking about them and their past, it's there. You automatically become very involved and included into their life. That's what I think it does. It makes that easier to make it more than just the patient-physician relationship. It makes you feel empathetic. I think that's a big deal. I don't think you have to do it. It happens on its own with this process. Rodolfo Estrada, MD, FCCP: Another aspect I think is important is that the patients when they show up to a provider, they have an expectation of something from that visit. Sometimes, the provider may give medications, but with the First 5 Minutes, you can also give them a space for the patient to actually share their journey and share their experience. The patient visit becomes complete when the patient is fulfilled. I think the providers will be more comfortable at times not prescribing medication because their role has been fulfilled through that visit. I think that will actually allow for these patients with pulmonary hypertension to be recognized earlier on, because the symptoms are pretty characteristic once their story is allowed to come to life. I think that's what the First 5 Minutes allow to do. Victor Test, MD, FCCP: We really want to develop this program so that it improves patient communication and trust so that we shorten this time to diagnosis. When I first began working in pulmonary hypertension, the average time to diagnosis was two and a half years from the onset of symptoms. In registries that are published after that, despite the increasing technology and awareness of the disease that time has actually increased into nearly three years. We need to actively work to change that from a pulmonary hypertension standpoint. But the First 5 Minutes is not just for pulmonary hypertension, it's for all lung diseases or really any disease. We want to shorten the time to diagnosis of complex lung diseases. Deborah Levine, MS, MD, FCCP: Where I think it's going to help the most is, obviously, with PH doctors or whatever the specialty is, asthma doctors or something. But actually with more generalized care either in the ER or the primary doc or even a community physician that is not in a specialized practice. I think that's where it starts and that's where a lot of the delay is, because patients come to us on inhalers that don't need inhalers because they don't have asthma. My thought is yes, I think it will help all of our teams. I think even more than that, it will help us if we can get this type of practice out to more of the general community. Even in the ER, you can take five minutes and get a good history, because maybe this is not what they have and maybe this is. Rodolfo Estrada, MD, FCCP: What I think about the First 5 Minutes in the pulmonary hypertension space is that these patients go through a lot for a very long time. It's not just the patient, but their community, their work, their families. The First 5 minutes allows the provider and the priority system to understand that dynamic a little bit better. It's not only the outcome of being able to walk more or mortality, it's what is the day-to-day looking like and how do we make that day-to-day better with interventions that we have available? Sometimes, those interventions are listening and being part of the journey with our patients, that conversation of empathy. Empathy is something that the provider and the system will feel once you start getting into a personal note with these patients that our system sometimes doesn't allow us as much. This is a tool to really bring that story to life and bring it into the space of conversation. Thank you for listening. My name is Rodolfo Estrada… Victor Test, MD, FCCP: I'm Dr. Victor Test… Deborah Levine, MS, MD, FCCP: I'm Dr. Debbie Levine, and we are 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/35538790

Episode 530 - First 5 Minutes® 07/22/2025

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

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

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