I’m Aware That I’m Rare: Dunbar Ivy, MD (472)

the phaware® interview

In this episode, Dr. Dunbar Ivy, a pediatric cardiologist at the University of Colorado, discusses the upcoming World Symposium on Pulmonary Hypertension, where experts from around the world will gather to discuss the progress made and future directions. Dr. Ivy highlights the work of the pediatric pulmonary hypertension task force, which aims to develop expert opinions on various topics, including the role of different therapies for patients who have failed all available medical treatments. The task force also focuses on understanding genetic abnormalities and developmental lung disorders, defining pulmonary hypertension in neonates, and addressing the challenges of clinical trials for pediatric patients.The task force plans to publish their findings in 2024 and welcomes feedback from the medical community.

Hi, I’m Dunbar Ivy. I’m a pediatric cardiologist at the University of Colorado in Denver, Colorado. I’ve had an interest in pulmonary hypertension for very close to 30 years. For me, it’s been a very exciting journey to see things move from really, no therapies, to one therapy to over 12 therapies. That’s really been exciting to be able to use some of those medicines off label, but I think they really have helped children and improve survival.

This year will be our next meeting of the World Symposium on Pulmonary Hypertension. It’s a meeting every five years or so. The goals of the meeting are to get experts from around the world in all aspects of pulmonary hypertension to bring together and develop ideas as to where have we come since the last meeting certainly, and also where should we go? What are the things that we need to keep working on? It’s exciting for us. I believe this is our third year to have a pediatric pulmonary hypertension task force. I think it’s really wonderful to see how far pediatrics has come.

There are eight clinicians chosen by the steering committee to meet and develop our own ideas and to write them down and to develop a paper so that we can share some knowledge. It’s important to note that they’re not guidelines. They’re sort of an expert opinion kind of document. The group is going to focus on several things. One is in patients who have failed all available medical therapies, what is the role of the Potts shunt versus an atrial septostomy versus lung transplant? Which patient would benefit most from which of those therapies? And is there a preferred order? Some of this I think really depends on the capabilities of the center, but we’ll try to provide some guidance in terms of which therapy for which patient.

Other things that we’re very interested in is there’s been really an explosion of interest in knowledge in developmental lung disorders from genetic abnormalities. The TBX4 mutation has raised a lot of interest in which patients have this, and it’s the second most common gene mutation and is interestingly found even in adults sort of later on or in newborn babies. So, there’s some exciting pathobiology that we need to learn about, for example, for that mutation, but also others.

We’re going to work on the definition of pulmonary hypertension in neonates. I think that’s well established in adults that they have a mean pulmonary pressure greater than 20 millimeters of mercury in an elevated pulmonary vascular resistance. But many of the patients that we take care of are neonates and we’re not able to perform cardiac catheterization on them. So, we’re trying to define some criteria that would be suggestive of an elevation of pulmonary artery pressure. Then, the key really is to say why is the pressure elevated? Is it from a left heart problem? Is it a right heart problem? Is it from pulmonary veins? Is it from intracardiac shunt, for example? I think there’s a need for that for some definition of pulmonary hypertension in neonates.

It’s a well-known and well respected conference. These are proceedings, again, they’re not guidelines. But I think they’re very well-read and I think that people take these recommendations seriously. From being on the committee for the last two sessions, we do get challenged on our thoughts, which is totally fine. But I think again, it sort of helps people to focus a little bit and to have a more clear definition of some things and directions.

One very, very important area is clinical trials for approval of medications in children with pulmonary hypertension. The approach is similar but very different between the US and Europe. I think there’s a higher standard showing a drug is effective in the United States, whereas in Europe, they tend to rely more on the adult trials for the efficacy. Then, they look at the pharmacokinetics, how the drug is metabolized and what the drug levels are in safety. Now, certainly we still do that in children in the States, but we’d like to have a common pathway for Europe and the US for drug approval.

One of the things that we will discuss is the challenges of enrollment. In order to get a drug approved in the United States, we are going to have to have enrolled trials. Right now, a lot of the trials are stopped early because they can’t enroll. So, there’s been a lot of thought about why that is. The design of the trials has changed so that I think families were very nervous about repeat heart catheterizations, for example. So those are not allowed in the trials anymore. Many of them will have a heart catheterizations as an entry criteria just to be sure that we know the right disorder. But then we’re looking for non-invasive ways to show that the drugs are helping the children.

I think the trickle down is that we always learn a lot from our adult colleagues. They have more evidence-based guidelines than we do. Ours are more experience-based. So, when I go to that meeting, I try to attend every session I can to learn from our adult colleagues. There’s 14 other sessions and one pediatric, so we’re in the minority, but it’s a very passionate group. I think all of us like going to the whole meeting and not just to the pediatric session.

These are the ideas that we have. We will continue to meet at least monthly to go through these ideas and work them out and see if we’re thinking about things correctly. Then, we’re pretty sure the manuscript will be published this year in 2024. So, we’ll be excited to get our ideas out there and also to get feedback.

My name is Dr. Dunbar Ivy, and I’m aware that my patients are rare.

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