Heart to Heart with Anna

How Research is Reshaping Lives in Congenital Heart Disease

• Paul Grossfeld (Guest), Anna Jaworski (Host), Sheri Turner (Producer) • Season 20 • Episode 472

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In this engaging episode of Heart to Heart with Anna, we dive into the significant strides made in pediatric cardiology, focusing on hypoplastic left heart syndrome (HLHS) and the inspiring journey of dedicated professionals like Dr. Paul Grossfeld. This episode highlights the complex nature of congenital heart disease, exploring not just the technical advancements in surgical techniques and post-operative care, but also the emotional journeys faced by families. Dr. Grossfeld shares powerful stories from his practice, illustrating the deep connections formed between healthcare providers and patients.

Listeners will learn about the critical role of early diagnostics and how modern medicine has transformed the fatality rates associated with HLHS. The episode discusses the collaborative efforts across medical disciplines, which lead to innovative treatment and significant improvements in patient outcomes. With a keen focus on the importance of research to address genetic and environmental influences on heart conditions, Dr. Grossfeld emphasizes the need for community support in fundraising and awareness initiatives.

As the conversation shifts toward the importance of heart screenings for athletes, listeners will discover how these measures can prevent tragic outcomes and promote healthy practices among young sports enthusiasts. We encourage our audience to reflect on their understanding of pediatric heart health and to become advocates for research and support within the community. Join us in this eye-opening episode that aims not only to inform but to inspire action among listeners who share a commitment to the congenital heart disease community. Subscribe, share, and engage with us to help uplift and empower those affected by these conditions.

Here are some helpful links mentioned in this episode:

HeartWorks: https://www.webuildhearts.org
Dr. Paul Grossfeld's charities: 
Light the Way: https://radyfoundation.org/get-involved/events/light-the-way/
Miracle Makers: https://radyfoundation.org/ways-to-give/fundraise/miracle-makers/
Hearts Unite the Globe (HUG): https://www.heartsunitetheglobe.com


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Dr. Paul Grossfeld:

There's just exhilaration, I guess, of just the pure beauty of what this organ does. So, combined with research and loving to take care of patients, it's just really become my calling.

Anna Jaworski:

Hi everybody. I'm so excited to talk to you in Heartland February 8, 2025. We have a great show. You've already heard the opening clip with Dr Grossfeld and I can't wait for you to meet him and to learn more about the amazing things that he's doing. But before that, I wanted to share with you a project that I'm working on.

Anna Jaworski:

Many of you know that I am an author. My first book was Hyperplastic Electrolytic Syndrome A Hamburg for Parents. That's the book I wrote after my child was diagnosed with HLHS and I was doing a ton of research on the different surgical treatments and the medications used, possible complications, and I just found that I was so stressed out I was afraid that I wouldn't remember everything. So I put together a book and I just found that I was so stressed out I was afraid that I wouldn't remember everything. So I put together a book and I decided after I was done that I really needed to make it available to other parents. Just like me.

Anna Jaworski:

My loyal listeners have heard Hope come on the show before. She came out as trans and talked to us about what that meant to her and how she was living with her CHD and her gender identity, so I felt that there needed to be a book about that and that I wanted to share very personal stories about how this affected my family and why I am the way I am, how my past has informed, the way that I have handled things, and I already have a publisher who's interested in it, hoping I'm going to write the book together. But that ended up not working out and now I'm focused on writing it myself and today I decided, hey, maybe I would save some time if I just dictated the book into one of the programs that I use. So I did that and I was talking about an event that happened many years ago and I got really emotional. I could feel the tears in my throat. I had my eyes closed while I was dictating and as soon as I opened my eyes and I saw what the program was writing, it completely took me out of the moment because the program did not understand me when I got emotional and it put out gibberish. So I ended up stopping my session and having to edit everything that I had recorded up until that point because it really didn't understand everything. I was saying that was a failed attempt, but I just thought maybe it would be interesting for you to hear some of the other things that I have going on.

Anna Jaworski:

Hope and I will be going to a writer's conference in March and I'm hoping to have the first two to three chapters fleshed out by then. We'll be meeting with a publisher who has expressed interest in her fantasy series and in my memoir. I will keep you posted on how that is progressing. And now on to the news. It is Heart Month 2025, and this is a really special time because this week, on Thursday, there is going to be a virtual dinner that will take place all across the globe.

Anna Jaworski:

I have been going to this virtual dinner once a year with my husband since it started and I'm super excited that we'll be attending again this year. It's really cool. It's a Zoom call so you can see the little boxes with different people who are preparing their meals, along with the chef and all of us sitting down and breaking bread together. It's a really special event that happens once a year and it's for one of my favorite nonprofits, heartworks, and my loyal listeners have met Tim Nelsick, who is one of the founders of HeartWorks. We'll learn a little bit more about HeartWorks. We'll meet some people behind the scenes. We'll have this amazing chef who will be preparing salmon tacos. I just printed out the menu and shopping list so that Frank and I can be preparing the meal with everybody else. I didn't get my registration in on time to have the box sent to me this year. I don't know what I was thinking. I was late in registering, but, folks, it's not too late for you to register and then you can get the email, just like I did, and you can still prepare the food along with everyone else. You just won't get the box with the bottle of wine, which is fine, because what really matters is that we're all sitting down together. We're all here to learn more about congenital heart disease and to try to find a cure, and that is what HeartWorks is all about. This is their number one fundraiser, and you don't even have to buy the box to participate. I just made a donation, which is what I do every year anyway, and it's not too late for you. Go to wwwwebuildheartsorg. I'll put the link in the show notes, you can register for the event, you'll get an email that has the recipe and the shopping list, and then I'll see you on Zoom. I'm super excited to be part of that this year, and this year they have a sale at auction as well. They have a beautiful 18-karat diamond fashion necklace that you can put a bid on if you so desire. It's just another way that you can support this really remarkable nonprofit organization that is determined to find a cure for congenital heart disease. I hope to see you there.

Anna Jaworski:

Now on to the show. Welcome to Heart to Heart with Anna. I am Anna Jaworski and your host. I'm also a heart mom to an adult who was born with a single ventricle heart and who is 30 years old. That's the reason I'm the host of this podcast.

Anna Jaworski:

Dr Paul Grossfeld is with me here today and he is a renowned pediatric cardiologist and researcher specializing in congenital heart defects. A professor of pediatrics at UC San Diego, he leads a research lab focused on genetic mechanisms underlying conditions, not just hypoplastic left heart syndrome, and that's what caused me to meet Dr Grossfeld many years ago was our interest in HLHS, or hypoplastic left heart syndrome. Dr Grossfeld has authored chapters in five medical books and received grants from the National Institutes of Health or NIH and the American Heart Association for his research. Over the past 25 years, he has been invited to speak at prestigious international conferences, sharing his expertise worldwide. Dr Grossfeld served as the medical leader for annual cardiac surgical missions at the Anchor Hospital for Children in Thimwe, cambodia, from 2006 to 2015, demonstrating his commitment to global health initiatives. He has also served as a cardiology consultant for the United States Olympic volleyball program for the past 14 years.

Anna Jaworski:

It blew my mind to read that. What in the world got you involved as a cardiology consult? I'm a little concerned. Do all of the Olympic teams have to have a cardiologist? How did this happen?

Dr. Paul Grossfeld:

I was actually moved initially when I was a medical student in Dallas when I came across a 15-year-old girl who had just had open-heart surgery to replace her aortic root. It turned out she had a very rare genetic syndrome called Marfan syndrome, which predisposes one to having a weakening of the aorta and a dissection. Just after that, the top women's player on the US Olympic volleyball team, a lady named Flo Hyman, was playing in a match and she collapsed and died suddenly on the volleyball court from an acute dissection of her aorta.

Dr. Paul Grossfeld:

Nobody knows in retrospect that she had this rare condition, which is relatively common in tall, thin people with long ears and long wigs.

Anna Jaworski:

Which is common with Mark Band syndrome?

Dr. Paul Grossfeld:

Yeah, Right and a volleyball player or a basketball player has exactly that kind of apatous sometimes. So years later I learned that even after that tragedy they weren't doing the type of screening that would have actually prevented her from dying. And so I reached out to the medical staff for US Olympic volleyball and they really embraced our efforts to basically create together a comprehensive cardiac screening program for their athletes to prevent any such tragedies from happening again. And actually we identified one player who happens to be here from San Diego and that marked the end of his volleyball career. He's actually having open-heart surgery electively next week as we speak.

Anna Jaworski:

Oh my gosh Wow.

Dr. Paul Grossfeld:

So you know it's been a gratifying program just in terms of being able to give back, but it's been really beneficial to US volleyball.

Anna Jaworski:

Wow, I was not expecting that story. That is amazing. I can't believe somebody could make it all the way to the Olympic level and they wouldn't have been screened for this. You would think that that would be something that all athletes who are at that level would have done.

Dr. Paul Grossfeld:

The US Olympic Committee's recommendations are pretty superficial, to be honest. In fact I'm on the committee of the American College of Cardiology California chapter for the prevention of sudden cardiac death in athletes and it's kind of an evolving process to come up with guidelines. The logistics can become a bit cumbersome but certainly for at-risk populations like maybe basketball players, volleyball players, in not even an hour's time we can do a history, physical screening, ekg and screening echocardiogram which is highly informative and really impactful in terms of hopefully identifying anyone at risk and preventing any such tragedies.

Anna Jaworski:

Yeah, I mean there's long QT syndrome and there are so many other conditions that we know people frequently are not diagnosed with until it's too late. So to make it to such a high level of athletic competition and this is the number one birth defect, as we know, for a certain percentage of the population, including my child and my producer's child, it can be life-threatening.

Dr. Paul Grossfeld:

Absolutely.

Anna Jaworski:

Wow, so did not expect to start the show off that way. See what happens when I don't talk to you in 20 years.

Dr. Paul Grossfeld:

We got some catching up to do, don't we?

Anna Jaworski:

You go off and do something with the Olympic board. Who knew Dr Grossfeld? But I did not expect for the show to start off with that, but what fun to know that there you are because you loved volleyball and you have turned your love of volleyball and your life's passion being a cardiologist into a way that you stayed to life with what you did, just being a volunteer and helping out that way. That just amazes me.

Dr. Paul Grossfeld:

That's cool and we've actually published just on our experience now with, I think, about 200 of the athletes, men and women, several peer-reviewed publications now that are useful to share our experience and allow others to hopefully come up with similar guidelines.

Anna Jaworski:

Yeah, here in Texas we have lost a number of athletes and there are some families who have taken it upon themselves to get AEVs in the school and to train people how to use them, and this is something that, at a grassroots level, we need to let everybody know about, and we need to be prepared, because these are situations where death could be avoided, and they need to be Funny.

Dr. Paul Grossfeld:

You should speak on Anna, because I'm actually very actively working as we speak to create a all-inclusive training program for at least high school students to learn how to do two things, what we call curbside CPR, so if you just happen to witness someone in a cardiac arrest and also how to use AEDs and we're actually you can start high school as a test program. But they have been incredibly receptive to embrace this effort. We're teaming with some of my colleagues from an organization called Project Adam, which you may be familiar with.

Anna Jaworski:

I am familiar. I had a nurse on my show who talked about that. Project Adam is amazing and they're doing such a good job of raising awareness in the schools. That's what we need to do is raise the next generation to be aware. Yeah, you can't just have select groups.

Dr. Paul Grossfeld:

Initially, I think when I heard about this, they were recommending just the athletes, but you have to train everybody, and the other component of this is to have what's referred to sometimes as an emergency medical response team on site of the school, and basically what that entails is ensuring that on every wing of every part of the school facilities there are a couple of faculty that are competent in CPR CPR trained we are blessed.

Dr. Paul Grossfeld:

At my son's high school, a public high school, they have 12 AEDs on site, so the idea is that what we're hoping to establish is not just training the kids, but also to make sure that there is an emergency medical response team that can respond with AED in hand in literally a matter of seconds, and, as you know, it's seconds that really counts.

Anna Jaworski:

You don't only want to have it with the athletes, because then if they're off at a game or something and the AED is either with them or locked in the director's floor, nobody can get to it. So having multiple AEDs around a school and teams who are trained for what to do is just amazing.

Dr. Paul Grossfeld:

I think just raising that level of awareness and having a plan in place. Raising that level of awareness and having a plan in place, the pieces are there, it just has to be organized and coordinated, but I am certain that this will be very impactful, combining with maybe more sophisticated screening programs in the future, like we just discussed.

Anna Jaworski:

Yeah, we do need to have more screening programs. I commend you for what you're doing. I think that's great. Starting with your son's high school is great, and then hopefully that will become a model for other schools in that school district and then beyond. Wow, that's just amazing.

Dr. Paul Grossfeld:

Yeah, that's exactly right.

Anna Jaworski:

I'm just amazed to hear all this stuff you're doing the Olympic team and the Project Adam which is amazing. So tell me what it was that started you on this path become a board certified pediatric cardiologist. We've kind of skirted around that and tightened up what you're doing now, but I want to go way back when and find out what got you interested in this to begin with.

Dr. Paul Grossfeld:

Well, I'd be divulging my age if I tell you how many years. It was good. There was never any eureka moment where I just woke up and said I'm going to be a pediatric cardiologist. Nothing like that. My parents were both social workers, but they also had a lot of interest in science and how things work and the human body. One year they got my brother and me a microscope when I was about eight years old, and I'll always remember this because this just illustrates a culture that I was brought up in. My dad, the social worker takes a pen and pricks his finger to get a drop of blood. He puts the drop of blood on the slide and shows my brother and me what human red blood cells look like, and I'll always remember he said something like guys, this is like the miracle of life. So that was the atmosphere that was instilled in us.

Dr. Paul Grossfeld:

My brother ended up being an architect and then when I went to college, I had a major called molecular, cellular and developmental biology. I didn't know for sure, but I was leaning with this sort of wait-and-see approach if medicine was going to be a good fit for me, and during that time I also got to spend a number of semesters, thanks to my teacher's aid from my freshman biology class, getting exposed to some cool basic science, molecular biology research and so during those few years I had the education in molecular biology and at the same time I knew I didn't want to be a chemical engineer, and so I thought medicine would be a nice fit, combined with research. That took me to Dallas, where I was going to medical school as well as graduate school for nine years, and as part of that experience I was really fortunate to get to spend some time working in the lab of two people that you might know, michael Brown and Jill Goldstein. They are both physicians trained in internal medicine, but physician scientists trying to learn more about why, at a frequency of about one in a million, a five-year-old child dies from a heart attack with completely blocked coronary arteries. And what they went on to discover is initially, for one thing, these children one in a million had a cholesterol level of like a thousand.

Dr. Paul Grossfeld:

And Mike and Joe went on to win the Nobel Prize in, I believe, 1985 in physiology or medicine for their pioneering work elucidating the whole pathways for how cells either take up dietary cholesterol or synthesize their own. And two things really to this day resonated with me from that approach really to this day resonated with me from that approach One is as physician scientists. They made sure that they had a very multidisciplinary group of investigators, both PhDs and MDs and MD-PhDs, who all brought a different perspective to the table to study a complex human disease like, in this case, familial hypercholesterolemia, and I should say that their work led to the development of now what is the world's most frequently prescribed drug Lipitor.

Dr. Paul Grossfeld:

So that was a model which I have tried to embrace. The other thing that is really important is by studying something that was very rare, the hope was that what they learned from that rare situation might apply to a much broader general population of patients and clearly that was the case and I would dare say in my case, for what I'm studying, starting with a very rare genetic syndrome, that it would hopefully apply to the broader population of all children with various types of congenital heart defects. So that was my background for getting interested in that. I actually thought I was going to want to do internal medicine until the first day of my internal medicine rotation as a third-year medical student and I quickly realized that I really didn't want to spend the rest of my life taking care of a patient population where, to a large extent, they didn't want to take care of themselves. So I vividly remember going home that Christmas break in the middle of my third year in medical school, feeling pretty lost actually, because all that time I thought I was going to want to do internal medicine, following in the footsteps of Mike and Joe, but that clearly wasn't the case. But what is a blessing to me is that it turned out.

Dr. Paul Grossfeld:

My next rotation was in pediatrics and I will always remember, bless his heart, chuck Ginsberg, the then chairman of pediatrics at UT Southwestern, took the four of us medical students aside that were just starting the rotation and he said something like guys, pediatrics is so amazing because you're treating patients that are on the beginning of the life curve, and that just resonated with me. So that was really cool. I knew I wanted to do pediatrics and I knew I probably wanted to pursue some specialty. At that time because of my rotation in Dallas, they encourage you as a fourth year medical student to do some away rotations at places that you might want to end up doing your residency at, and so I ended up getting a rotation in San Diego, which was one of the places I was interested in.

Dr. Paul Grossfeld:

As fate would have it, the only opening that they had for me was pediatric cardiology. I actually wanted to do pediatric infectious disease because I thought that was obviously relevant. When they told me that the only thing they had was pediatric cardiology, I literally remember feeling quite disappointed by that. But sure enough, I got into that and almost overnight realized it was just absolutely my calling of pediatrics and clinical medicine, which is really clinical developmental biology. That's what congenital heart disease is. It's the problem in how the heart develops, and that really resonated with me. That's what took me to get to where I am now. You just have to keep an open mind and you just never know where life's just going to take you.

Anna Jaworski:

Yeah, absolutely so. What got you interested in hypoplastic left heart syndrome?

Dr. Paul Grossfeld:

When you look at all the congenital heart defects, to this day hypoplastic left heart syndrome is still the most common cause of death in all infants with any type of congenital heart defect. So it's a huge clinical problem Number one. I've taken care of a number of these patients over the years, which is really inspiring. But the other aspect of it is when you think about the biology. I mean, how does a heart develop and what is it that goes wrong? 98, 99% of the time the heart develops perfectly, which is incredible when you think, Isn't that the miracle?

Anna Jaworski:

To me, that's the miracle when you see it starts out as a tube. It starts out as a tube, but it's somehow. It twists and turns and forms.

Dr. Paul Grossfeld:

It's just incredible. You reminded me of one of the most memorable experiences I've ever had in my career and that was back when I was, I think, a fellow. I got to scrub in and actually assist our surgeon doing an open heart surgery on a child. And in the process of getting the baby off of the heart-lung machine, they begin to warm the body so that the timing is just right to decannulate. As that process is happening, of course, during the actual surgery the heart is completely stopped and what I observed during that process of warming was spontaneously that heart starts beating again.

Anna Jaworski:

Amazing.

Dr. Paul Grossfeld:

And there was something so magical about that life force and that heart. There's just exhilaration, I guess, of just the pure beauty of what this organ does, so combined with research and loving to take care of patients. It's just really become my calling.

HUG Message:

Heart to Heart with Anna is a presentation of Hearts Unite the Globe and is part of the Hug Podcast Network. Hearts Unite the Globe is a non-profit organization devoted to providing resources to the congenital heart defect community to uplift, empower and enrich the lives of our community members. If you would like access to free resources pertaining to the CHD community, please visit our website at wwwcongenitalheartdefectscom for information about CHD, the hospitals that treat children with CHD, summer camps for CHD survivors and much, much more. You are listening to Heart to Heart with Anna. If you have a question or comment that you would like addressed on our show, please send an email to Anna Jaworski at Anna at hearttoheartwithannacom. That's Anna at hearttoheartwithannacom. That's Anna at hearttoheartwithannacom. Now back to Heart to Heart with Anna.

Anna Jaworski:

Dr Grossfeld, when you first began your research, HOHS had an extremely high fatality rate I know because that's when my kid was born and medical literature from 2000 actually shows survival rates of 63 to 80 percent at one year and 58 to 72 percent at five years. So can you tell us about the mentors or colleagues that you worked with who guided and supported you in your early work, and how their percentages have really improved since the 2000s?

Dr. Paul Grossfeld:

I think there have been several advances along the way that have fortunately gotten us to the point where, even though the three-stage surgical approach is still a palliation, we've gotten so good over the years now with some important criteria for patient selection that I think it's almost bordering on unethical morally to not offer surgery or to maybe put it in another way.

Dr. Paul Grossfeld:

I think it's almost unethical in a good candidate child to offer no care, although that's debatable Nowadays. In most cases this specific heart defect is diagnosed prenatally, and that's really important because it gives us the ability to proactively plan for the delivery and to monitor closely during pregnancy. So that's already a huge step forward. Surgical techniques certainly have evolved over the years, specifically for hycoplastic left heart or single ventricle surgeries in general, not just the surgeons themselves but also the anesthesiologists creating really successful cardiopreservation during cardiopulmonary bypass. And then another really important component is how sophisticated we have become in our postoperative care.

Dr. Paul Grossfeld:

Back when I was there wasn't even a specialty called pediatric cardiac intensive care and now the standard is people that take care of these babies have specific training and are extra board certified in pediatric cardiac intensive care. So that has also been a leap forward. We now have specialized pediatric cardiac intensive care units specifically for managing these patients. We also have ECMO, extracorporeal membranous oxygenation basically to allow the sickest of patients to recover and stabilize, which we didn't have maybe 30 years ago. So I think it's a combination of those factors. Along the way I've had some really extraordinary clinical mentors. My division chief, abe Rothring, when I was a fellow, was phenomenal. The other person who really is the father of pediatric cardiology as we know it in San Diego is also a very dear close friend of mine, john Lamberti.

Anna Jaworski:

Oh yeah, you can't do any research without seeing his name and being familiar with him. Wow Right.

Dr. Paul Grossfeld:

Over the years. I think my philosophy is check the ego and just try to surround yourself with the best possible people. Ego and just try to surround yourself with the best possible people. And those are certainly a couple of significant examples in my clinical training, for sure.

Anna Jaworski:

One of the things that has amazed me in pediatric cardiology is how tight all of you doctors are. You all know each other and what I have seen is doctors don't seem to be afraid to pick up the phone and say hey, I've got a kid with this, what do you think? And there seems to be so much collaboration in this field. Is that unusual?

Dr. Paul Grossfeld:

I think it's institution specific, but for sure, when you think about the team, the sort of limelight person is the surgeon, right? It's kind of like a television news broadcast, you have the broadcasters. Person is the surgeon, right? It's kind of like a television news broadcast, you have the broadcasters, but then you've got a whole team of people operating behind the scenes or maybe at the forefront as well, and so it has to be collaborative. There's just no other way that it can work.

Anna Jaworski:

Yeah, but I think even between institutions it seems like years ago I used to hear a lot of rumblings of oh, don't take your child to this hospital, take your child to that hospital. And people being almost like secretive with the research they were doing because they wanted to be the ones to get credit and those doctors wanted their names on whatever procedures. I'm not just talking pediatric cardiology, I'm just talking medicine in general, but I haven't seen that with pediatric cardiology. I'm just talking medicine in general, but I haven't seen that with pediatric cardiology. Maybe it's the people who are attracted to the field.

Dr. Paul Grossfeld:

Yeah, I would agree with that, although I would have to say that unfortunately, there are certain other factors that sometimes lead people down paths that sort of use their way in terms of what our real calling is. As an example, the US News and World Report rankings in some ways do a service. Look, if I have a child and I know that they need open heart surgery, I'm much more likely to want to ideally take him to a higher range place than number 100. But having said that, I think honestly I've seen just around the country programs that I think put too much emphasis on US News and World Report rankings. I think a couple of years ago Harvard Medical School actually dropped out of that and the dean in the medical school was quoted as saying something to the effect that sometimes so much effort is spent on US News and World Report rankings that is at the expense or the compromise of patient care. So I think we have to have a balance.

Dr. Paul Grossfeld:

But I would say to your point that it's a group of people that are, by and large, doing it for the right reasons and it's a team effort and, like any other team, there are dynamics that go into that and when people treat each other with respect and are able to check the egos and say what do you think about this patient of mine or what do you think about this surgical approach? This is an example. Every week we discuss our surgical patients and just to make sure that as a team there is a consensus of what the right next step is. So it is intrinsic to success to have that kind of collaborative culture.

Anna Jaworski:

Yeah, I would agree. One of the things that I'm encouraged by, as a heart mom, is the multi-institutional collaborations that are going on, and I just had Dr Timothy Nelson on my podcast. You know, dr Nelson.

Dr. Paul Grossfeld:

Very well we collaborate.

Anna Jaworski:

See, there you go.

Dr. Paul Grossfeld:

You just took the words out of your mouth.

Anna Jaworski:

Prime example of what I'm talking about, and this gives me so much hope, because it doesn't matter if you're at Boston or Philadelphia or San Diego or San Antonio, Texas, which is where I was when you have this nationwide collaboration and in some cases it's worldwide collaboration that's going on. That's where the real innovation comes in and that's where you can see tremendous changes for the betterment of the patients.

Dr. Paul Grossfeld:

Can I give you an example specifically involving Tim.

Dr. Paul Grossfeld:

Tim has been extremely successful in getting the support from the Wannick Foundation to hopefully develop stem cell technologies to extend quality and quantity of life of single ventricle patients.

Dr. Paul Grossfeld:

So along the way, what they've done is collected patient families now over 200 patient families, so hypoglossic vector heart patients and their families and it's extraordinary because they have very detailed clinical information on everyone in these patients.

Dr. Paul Grossfeld:

They've also done all genome sequencing and bottom line is, with this group of over 200 patients there's a whole range of outcomes and actually one of the things I'm embarking on that would not be possible without Tim is to use this very exciting technology called induced pluripotent stem cells to reprogram cells from patients with a specific disease, in this case hypoclastic left heart syndrome, to now allow us to, thanks to a company that I'm working with, an academic spinoff company called NovoHeart, they're actually going to do bioengineered tissue, create bioengineered heart tissue from these patients and, instead of waiting till 10, 20 years when they start developing heart failure for whatever reason, we will at the outset hopefully be able to prospectively stratify these patients by doing these functional studies up front, based from an infant, and that will allow us to identify those that will be at increased risk, let's say for early onset heart failure.

Dr. Paul Grossfeld:

So for those patients we're going to treat aggressively with medications, we're going to have a lower threshold for listing for transplant, because the way it is now, they're also thrown into the same clinical bucket of single ventricle. Let's do these surgeries. Certainly, as we talked about, the outcomes are better, but we really don't know from the outset who's going to do well and who's not. So this way we think, with this much more personalized precision medicine approach, thanks to collaboration from people like Tim Nelson, we can join forces and I really think this is going to transform how we take care of single ventricle patients in the future.

Anna Jaworski:

Absolutely and hopefully not just single ventricle, but this will have a ripple effect and we'll see this happening with tetralogy of fallot and transposition and the great vestals and some of the other syndromes as well. We know that HLHS is complex, but there are other genetic syndromes sometimes that are tangentially associated with it, like I've actually heard of some people with HLHS who are Down syndrome. I know you've done a ton of research on Jacobson syndrome and there are other syndromes as well. Can you tell me about how some of these other syndromes as well? So can you tell me about how some of these other syndromes are associated with HRHS?

Dr. Paul Grossfeld:

Right.

Dr. Paul Grossfeld:

Historically in the literature there are a few that have been associated somewhat with hypoplastic left heart syndrome, like trisomy 13, trisomy 18. When I was literally in my first year of my pediatric cardiology training in July of 1995, I happened to come across a patient with sort of a form of hypoplastic left heart syndrome that did have a very rare genetic syndrome called Jacobson syndrome and in that patient's chart was the original paper describing the syndrome, which is due to the loss of the piece of chromosomal left hand. So that was incredibly powerful because, remember, back in 1995, we didn't have much in the way of technology, but it did clearly establish, and I was able to determine in the next few years, that something like close to 10% of children born with Jacobson syndrome have hypoplastic left heart syndrome and that was at the time probably a higher frequency than any other known genetic syndrome. And so, kind of paralleling what I described to you before with Mike and Jill and their phenomenal work on hypercholesterolemia, my hypothesis was, if we can learn what the genetic causes from within chromosome 11 of hypoplastic by heart syndrome in this very rare set of patients, then maybe that's going to have much broader application. And that has clearly been the case, and even what I just described to you with our collaboration with Tim Nelson, really would not have been possible were it not for the insights that we've already established by studying Jacobson's syndrome and hypoplasmic blood hurt.

Baby Hearts Press:

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Anna Jaworski:

Dr Grossman, I'm just fascinated by all the research that you've done, but I know that doing research like this is pretty tough. What's the biggest obstacle you've done, but I know that doing research like this is pretty tough. What's the biggest obstacle you've had to the research that you've done?

Dr. Paul Grossfeld:

Without a doubt, the biggest obstacle is just to have sustained funding, and it's shocking that here I am studying the most common cause of death in the most common form of birth defect, and it's still been really challenging to get funding from some of the established funding mechanisms like NIH and the American Heart Association. I have been blessed, to be honest, to have some grateful patient families and foundations that have stepped up to support me that without their support we wouldn't be having this discussion today. That has certainly been the most challenging and no doubt keeps me up at night more than anything. At this time last year I was literally five months away from having a shutdown on my land, despite having two very top tier peer-reviewed publications in the year preceding that. It's a really complicated process, but philanthropy has actually now replaced the NIH as the most common source of funding for biomedical research in this country.

Dr. Paul Grossfeld:

Sometimes it's not considered as glamorous, but it is. As my former division chief said to me, money is money. People like yourself, anna, who have skin in the game and are so passionate about the cause, that's what it takes and that's where most of my work is actually. On a much more sustainable level, craig Thomas and his wife, rebecca Milkman. Craig and his wife have a child with Jacobson syndrome who had heart surgery as a baby. Craig was the co-creator of the very successful television series called how I Met your Mother. They reached out to me and they had done some extraordinary fundraising efforts. Twice during the time that the show was still in operation, they had a fundraising event on the set with all the cast and the crew of the show.

Anna Jaworski:

Wow.

Dr. Paul Grossfeld:

And since then, every year at this time of year we have a fundraising online campaign to raise funds. So I have figured that just through their efforts alone over the last 15 or so years they've raised single-handedly over $1.5 million.

Anna Jaworski:

just for my research, that should make you feel good, that should help you sleep at night. And yet, despite all that funding, five months ago it almost shut down.

Dr. Paul Grossfeld:

There was a combination of circumstances a few years ago, right with the pandemic and inflation and everything else that really put the squeeze on things.

Dr. Paul Grossfeld:

In fact, I had to let go a couple of years ago of one of the PhDs working in my lab because I saw the writing was on the wall. I was going to have to tighten the belt, which was the right decisions. $250,000 a year doesn't sound like a lot until you have to start fundraising to get that. In terms of the other greatest challenge, aside from the financial component, we'd still like to have a really good genetically engineered mouse model for hypoplastic left heart syndrome. We have not been successful in that up until now, which honestly I think is just a reflection of the complexity of the genetics of hypoplastic left heart syndrome. So we keep learning and actually we think we may be very close now with some new insights that we've gained pretty recently. Time will tell, but we have to have a really good animal model, which has been part of the problems in the field that there really hasn't been a reliable one up until now, particularly in the mouse, which is the gold standard.

Anna Jaworski:

I remember when I met you, you were part of a forum that had a lot of parents and we used to pepper you with questions, and one of the big questions that we would ask you and any other doctor who happened into that forum was is it genetic?

Anna Jaworski:

Is it something that I did wrong or that's part of my family dynamics that we just don't know about?

Anna Jaworski:

And at that time 20 some odd years ago when I first met you, there was a lot of discussion about no, we don't think it's genetic. My own doctor told me oh no, this is just a freak of nature which does not feel right. But it seemed like there was some research that was done that said maybe some people have a genetic predisposition, but there's probably some environmental mechanism that's also going on that's causing this to happen more. In fact, I remember quite a few years ago there was a study that was done in one particular hospital, because there were several nurses that all worked in the same hospital I think there were three of them that had babies with hypoplastic left heart syndrome, which is very strange and the CDC went to see if there was some kind of environmental circumstance in that particular hospital and it came up with nothing, which is frustrating because we all want to know what is causing HLHS. Are you saying that there is a genetic cause for HLHS?

Dr. Paul Grossfeld:

It's very complex, which makes it really interesting and very frustrating at the same time. So let me give you a little bit of background on that. If you look at something like DeGeorge syndrome, right, so that's due to the microdeletion in 22q11. For certain specific heart defects, like a form of Tetralogy of Fallot, with what we call a right-sided aortic arch or some of the other conal-troncal defects, as we call it, right-sided aortic arch or some of the other colonotronchal defects, as we call it, is as high as 50% of those cases are due specifically to one genetic cause the microdeletion in chromosome 22. What Tim Nelson's program has shown, through doing whole genome sequencing now on over 200 patients with hypoplastic left heart syndrome, is there are no low-hanging fruit like for DeJoris. Having said that, there are specific genetic causes that are clear, like chromosome 11, 11q. But having said that, I can have two patients with the identical chromosome 11 deletion and one patient will have full-blown hypoplastic left heart syndrome, the other patient will have a normal heart.

Dr. Paul Grossfeld:

The couple of genes that we've identified, we are sure are genetic predispositions to hypoplastic left heart syndrome and, for that matter, other complex heart defects. But there are multiple factors clearly involved. First of all, it is never any parent's fault. I tell parents, you have as much control over that as you do the color of your kid's eyes, so don't ever beat yourself up about any kind of cause. There may be environmental interactions. The Baltimore Washington Infant Study Group from many years ago showed, for example, that there is an association with parental exposure to organic solvents giving something like a seven-fold higher frequency of hypoplastic left heart syndrome.

Anna Jaworski:

What is an organic solvent.

Dr. Paul Grossfeld:

Things that are used for cleaning, like commercial industrial cleaners, that kind of thing.

Anna Jaworski:

Cleaners that might be used in a hospital. Man.

Dr. Paul Grossfeld:

That's a really interesting thought. Possibly when you hear about these clusters it's highly suspicious, right. So it takes a lot of resources to take the deep dive to figure those causes out. But yeah, it wouldn't be surprising and even for what we know now it's certainly plausible that, for example, if cells have to migrate during the developing stages in the heart to get to where they need to go, if you have some environmental toxin that literally poisons those cells at just the critical time during heart development, you could easily envision that sort of interaction between genetics and environment. But even with the genetics, we think there are now some conserved pathways that are required in heart development where any step along the way it might affect the development of the heart. But I think it's kind of like a roll of the dice genetically you just have to have the right combination of factors for each parent. But unquestionably there is a very strong genetic component for us of heart syndrome.

Anna Jaworski:

Okay, you're the first person to say that to me.

Dr. Paul Grossfeld:

I'm surprised right now.

Anna Jaworski:

Well, I think it's taken a long time for somebody to be able to definitively say that there is some kind of genetic component. I do remember when I was doing research for my first book that I was wondering if there was a certain drug or chemical like you were saying, and I remember seeing that women who took lithium had a higher percentage of babies, particularly with HLHS, which I found surprising. So it makes me wonder what does lithium do to the body that might cause that? I think there have to be a number of factors.

Dr. Paul Grossfeld:

I agree.

Anna Jaworski:

I'm glad you agree with me. I wouldn't mind if you said, parents, this is not your fault, because I think a lot of parents worry.

Anna Jaworski:

I had a perfectly heart-healthy child from my first child. Why is it that my second child had such serious problems and it wasn't diagnosed, even though I had three ultrasounds when I was pregnant? Because we couldn't agree on the due date of the baby and we didn't find out until it was almost too late, which is really scary. Things are different now, folks. My baby was 30 years old, so, yeah, things are a are different now, folks. My baby was 30 years old, so, yeah, things are a lot different now.

Anna Jaworski:

I think a lot more people are being diagnosed in utero, which has pros and cons. I can't imagine suffering through months and months of pregnancy knowing that my baby has something so serious wrong with the heart. On the other hand, look at what they're doing. What they're doing in utero procedures for babies with HLHS, which hopefully will allow babies to be born and have surgery who might have otherwise not been a good candidate for surgery, to offer parents compassionate care. And yet I do know that there are some babies who are born with such a severe case of HLHS where the baby's not a good candidate for surgery, and those parents shouldn't have to put their babies through surgery. I agree.

Anna Jaworski:

In my book I said I don't think that HLHS parents should be offered compassionate care, given there is a chance for hope. But now I've met enough parents over the last 30 years whose babies were not a good candidate. And why would you open a baby's chest up and put them through the pain that they have to endure when you know really there's not a good chance that they're going to survive, and you're going to cause so much trauma, not only to the baby but to the surgeon, to the whole surgical team and to the parents?

Dr. Paul Grossfeld:

Right.

Anna Jaworski:

A lot of trauma that goes on when you do something like that.

Dr. Paul Grossfeld:

I often tell my parents, being a parent myself, that I think in many ways it's more traumatic to the parents than the child. I mean your child does not remember when they had surgery as a newborn right, but you sure did, and I'm sure you're traumatized by that to this day.

Anna Jaworski:

That's true, that's absolutely true.

Dr. Paul Grossfeld:

It certainly was acceptable back then to offer comfort, care and let the baby go home and die.

Anna Jaworski:

This is the problem Even with the extensive research that has been done, we still can't conclusively say which kids are going to make it and which aren't. I had Dr Dawn Alardi on my program and she said the number one factor to determine whether or not a baby is going to be successful has nothing to do with their heart defect, the surgeon, the hospital that they're at that. The number one factor actually is the family.

Dr. Paul Grossfeld:

Not to be dismissed. The family is huge and it doesn't even matter necessarily specifically socioeconomically. What matters is parents that are able to put in the time, to be proactive, to be compliant, to show up for their visits on time and not come see me a year late. So all those factors contribute. But the project that I'm working on in collaboration with Tim Nelson's group is going to help to stratify and identify outcomes early on. To stratify and identify outcomes early on. So I'm very encouraged that this new precision medicine approach potentially will be transformational for how we manage such patients from the get-go.

Anna Jaworski:

That'd be nice. I'm glad to know that you and Dr Nelson are working together and that you might be able to find some factors that will help us to know if we need to be more aggressive with treatment or help parents be better prepared. For example, I had no idea that aortic aneurysms are not uncommon in people who have a Pontian heart until my own child developed an aortic aneurysm and after that, when I did research, I think I saw the research. Right now I want to say one in four.

Anna Jaworski:

It was a huge number of people who have a Fontan heart who can get an aortic aneurysm. I don't know. Would it have been better for me to know that could be a thing? I don't know? Because there's protein losing, enteropathy and there's plastic bronchitis and there are all these horrible things that can happen that hopefully won't happen to your child. But if we knew that there were certain factors or certain markers that, okay, your kid has this marker, only one in four ends up having this condition, but your kid has all the markers that your kid's going to be way more at risk.

Dr. Paul Grossfeld:

Well, the way I look at it, Anna is, I think it's going to be very similar to what's evolved over the last few decades for patients with HIV or type 1 diabetes. We're not curing those diseases, but we're making those diseases manageable with novel medical therapies, which again speaks to why it's so important to promote the research. So I didn't get a chance to tell you this, but we actually have shown in a fraud model that we could potentially prevent hypoplastic left heart in a fraud model, obviously not humans.

Anna Jaworski:

Wait a minute. You could prevent, in a fraud, the heart from becoming an HLHS heart. So how did you know it was going to be an HLHS heart to begin with, and where did you stop it and did you re-perstate? Okay, you have to tell me more.

Dr. Paul Grossfeld:

All right. So let me give you a little bit of background. One of two genes, actually, that we've discovered in chromosome 11 is a gene called ETS1. It's a transcription factor, so it radiates a whole sequence of genes that are expressed during various stages of organ development, including the heart. It turns out a wonderful collaborator of mine at Caltech, california Institute of Technology, has been studying the same gene because of its role in a specific population of cells that has a lot of functions in the development of various organs, including the heart, called neurocrest cells.

Dr. Paul Grossfeld:

She, with her postdoctoral fellow, a very talented junior faculty member by the name of Shui Ni she's at Georgia Tech. What she could do is specifically eliminate or knock down the expression of this gene in the developing fraud. And what we see is, again, this is a fraud. It's not a human, but the outcome of that is a hypoplastic ventricle. Now frog heart only has one ventricle. It's not a human.

Dr. Paul Grossfeld:

But then the other population of cells that this particular gene is expressed in, besides these neural crest cells, is a specific population of cells in the heart called the endocardium. It's an inner lining of cells. So when Shui originally knocked down this gene in the developing frog, she saw I actually pointed out to her because she had never heard of hypoplastic left heart, but I said, wow, that's an amazing connection because that is exactly what we see in the human condition in some cases. So that has become a model organism for us to begin to study some of these pathways. Shuey, by training, is an embryologist, and so one of the things that embryologists like to do is they graft regenerative tissue for various populations of cells, is they graft progenitor tissue for various populations of cells. And what she was able to show in the frog we had her publish this coming soon is when you knock down the skin and get the hypoplastic ventricle.

Dr. Paul Grossfeld:

If at the same time you do that, you graft progenitor tissue from a normal donor very early in heart development, you actually prevent the hypoplastic left heart.

Anna Jaworski:

So this would have to be before 20 weeks gestation.

Dr. Paul Grossfeld:

It would have to be really early.

Anna Jaworski:

Yeah.

Dr. Paul Grossfeld:

This is very early, and this actually speaks to a whole another component of our research.

Dr. Paul Grossfeld:

The dominant has been that in hypoplastic left heart it occurs relatively late in development due to impaired blood flow, for a variety of potential reasons, and that's definitely true for a sunset, but what I have always maintained and now we have stronger evidence than ever that in certain forms of classic hypoplastic left heart syndrome, it's actually due to something that arises very early in the developing heart.

Dr. Paul Grossfeld:

In the frog, experimental myeloderm, we see, first of all, this abnormal ventricle occurring very early, and this intervention that Shui has been able to do in the frog heart is very early. We're talking certainly well within the first trimester, if you were to compare it to humans early. We're topping certainly well within the first trimester if you were to compare it to humans. So one of the limitations right now is oftentimes this isn't even diagnosed until mid-gestation, 20 weeks. The other point, though, that I think is really important and this is why I think our research is so at the cutting edge is you mentioned before fetal intervention, if you go back and look at the initial studies published by Boston Children's, which is phenomenal what they've been trying to do. The fact, though, is that when they go in and try to relieve the obstruction of the abnormal aortic valve to prevent hypoplastic left heart syndrome from evolving over the subsequent part of the pregnancy, it's only a very small subset that respond and the vast majority of those initial patients went on to require the Norwood and the single ventricle palliation.

Anna Jaworski:

Well, sometimes four or more surgeries instead of the three that we normally had.

Dr. Paul Grossfeld:

And what that speaks to is borne out by our research that certainly for a subset of these patients, by 20 weeks the dye is cast. If you want to add any hopes of being able to intervene to actually prevent this, you've got to intervene much earlier and that's why I said that we're talking a decade or two away, because we have to have some way to actually diagnose this very early, when there might be that window of opportunity to intervene to prevent it. And we're not even close to that yet.

Anna Jaworski:

Okay. So I'm sure I'm going to have some listeners say wait a minute. The majority of his funding has been from private donations, from philanthropic donations. How can I donate? So how can people donate to your fund?

Dr. Paul Grossfeld:

Great. We have, through our foundation at Rady Children's Hospital, a donation campaign called Light the Way during the end of the year winter holiday season that people can donate to the rest of the year. There's another fund called Miracle Makers and bottom line is 100% of people's donations go directly to support my research lab at ECSD.

Anna Jaworski:

Don't worry, fred, I will find this and put it in a show notes so you don't have to do it. It'll be a lot easier that way.

Dr. Paul Grossfeld:

Thank you, that's the best way.

Anna Jaworski:

A hundred percent. That's amazing because you look at a lot of these other organizations and there's a certain amount of overhead and they have to take a certain percentage. So for 100% to go to the research, that's pretty remarkable.

Dr. Paul Grossfeld:

I'm very proud that ECSD and RADES have adopted that policy. For sure it's huge.

Anna Jaworski:

It is huge. It is huge that kind of giving will make, hopefully hypoplastic left heart syndrome. I think of the past. Wouldn't that be amazing? It'd be amazing if it could happen in your lifetime.

Dr. Paul Grossfeld:

Yeah, even to be able to stratify patients, to give them the personalized precision medicine therapies that they need or don't eat, would really be, I think, a major step forward. Because we just guess I don't know if your child was on glasses and drugs like ACE inhibitors there's controversy, we don't really know. We just do it because it makes us feel better and we think it might help. But do we actually know from patient to the next if they're going to really benefit from that? Not right now.

Anna Jaworski:

Yeah, there's still a lot of guesswork, but people like my daughter I'm trying to twist her arm into joining the biorepository that Dr Nelson is putting together because I told her, even though she's doing really well right now they need to know.

Anna Jaworski:

What is it about you that's helping you to do so well and possibly somebody else isn't doing so well, so the more data points they have, the better informed decisions we'll be able to make in the future. We need as many people as possible joining the co-op and being part of the biorepository, because it's still fairly rare. There aren't millions of people that have HLHS walking around, but there are enough that we could get some significant data gathered. If we have all of these different people from all over the world doing it and I know right now Dr Nelson is just focusing on the United States, but my hope is that eventually he'll be able to expand and become international as well. Like this, it would make a huge difference.

Dr. Paul Grossfeld:

Yeah, and when you're talking about a rare disease, you just have to get the numbers for sure.

Anna Jaworski:

You can't overgeneralize when you only have 20 patients in a study.

Dr. Paul Grossfeld:

That's why these kinds of studies have to be multi-center.

Anna Jaworski:

Thank you, dr Grossfeld, for coming on the program today, and thank you, sherry, for being my producer today. The two of you are amazing, Well, as are you, and I'm fangirling, dr Grossfeld. How do you like that? Now you should have your own bag, dr Grossfeld. How do you like that, dr Grossfeld?

Dr. Paul Grossfeld:

Thank you both. It's been a joy and I would love to do this again.

Anna Jaworski:

Okay, that is amazing. That does conclude this episode of Heart to Heart with Dana. Thanks for listening today. My friends, I hope you found this program helpful. If you have any questions about the show, please send them to me on the HUD website, that's heartsunitetheglobecom. There's a little form that you can fill out right there on the website and I'll put a link to it in the show notes to Light the Way and Miracle Makers. Just imagine if everyone who was listening to this show donated $5, like a cup of coffee for Dr Brosefeld. It would add up and you tell three people and then they tell three people. You know what. We could help make this research a reality, and that's what it's going to take. It's going to come from parents and doctors and people who care. I know if you're listening to this show, I know you care, so check out the show notes. Don't do it if you're driving, but as soon as you stop the links will be there. And have a wonderful day, my friends, and remember you are not alone.

HUG Message:

Thank you again for joining us this week. We hope you have become inspired and empowered to become an advocate for the congenital heart community. Heart to Heart with Anna, with your host, anna Jaworski, can be heard at any time, wherever you get your podcasts. A new episode is released every Tuesday from noon Eastern time.

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