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Dr. Kaushal: We at Lurie Children's are the leaders in stem cell therapy in congenital heart disease patients. We're carrying out currently two different enrolling clinical trials, both are at a phase two level. And we're also another phase one study in dilated cardiomyopathy patients.

Prakash Chandran (Host): Today, we're joined by Dr. Sanjay Kaushal division, head of cardiovascular thoracic surgery at Ann and Robert H Lurie children's hospital of Chicago and a pioneer leading to a future of better outcomes for children with heart complications. This is Precision, Perspectives on Children's Surgery, the podcast from Lurie Children's Hospital. I'm your host Prakash Chandran. So, Dr. Kaushal thank you so much for joining us today. I really appreciate your time. You know, in doing some research, it seems like you do everything from neonatal cardiac surgery, single ventricle reconstruction, biventricle repairs, and you also address adult congenital heart disease. So with all of this, what exactly is your specialty and how did you get into it?

Sunjay Kaushal, MD, PhD (Guest): Thank you. So my specialty is, that I'm a Pediatric Heart Surgeon that specializes in, congenital heart disease, condition that happens at birth. And sometimes it manifests itself with the heart disease early on as a baby or it can present later in life when you're 20 or 30 years old.

So, we in the field of congenital heart surgery, we can operate on any patient with this diagnosis. That is the specialty I have chosen. I've gotten here from a lot of training. I, just to give you a glimpse of what the training I've done. I went to medical school. That's four years. In between there, I got my PhD, so I have another four years tacked on to that. So, that's eight years. And then I did 10 years of training as a pediatric heart surgeon. First I had to become a n adult cardiac surgeon. And then you specialize into pediatric or congenital heart surgery, which is an additional one year. So that's a lot of training to get to where I am.

Host: Almost two decades worth. Wow.

Dr. Kaushal: Yeah.

Host: That's absolutely amazing and before we move on to the next question, I have to ask why so many years training, what makes you so passionate about the pediatric heart specialty?

Dr. Kaushal: Pediatric heart specialty is it's a very unique specialty. It's a specialty where you can change a little baby's life right from the beginning. Sometimes you can correct the congenital heart disease with one surgery or sometimes you have to do multiple surgeries to correct their condition. There is a great satisfaction to see how babies turn around very quickly after the corrective surgery. Their physiology changes, their activity level, how they interact with their parents. And some of the most striking examples is where, when is where a baby comes into the operating room blue and leaves the operating room pink and that is the most satisfying aspects of our job.

Host: So I understand you're doing some research. I'd love to understand a little bit more about the research you're doing specifically with stem cells and, you know, tell us how it works. Who does it help and how far into the trial you are currently?

Dr. Kaushal: So we've been working on new avenues or new innovations for babies with congenital heart disease. In particular, looking at ways of improving the function of the heart. And so, in doing so we've been studying cardiac stem cells and trying to determine if you inject these cells into the heart, can you improve function of the heart? And that is a very important concept and also treatment that can occur for many babies with congenital heart disease. We've been studying this for last 15 years. We've been first exploring whether they do occur or do they exist in the heart. And then trying to understand if we can use these stem cells in order to improve the function of the heart.

The way that these cells work, is that they remodel or reprogram the heart. So, when the heart is feeling sick and not feeling like it wants to work, it becomes tired. Subsequently, the baby becomes tired. So we're trying to introduce stem cells into that tired heart in order to improve the function of the heart, improve the ability of the heart to contract and pump blood to the rest of the body.

If we are successful, then these babies can be cured and can live normal lives. And that is what our purpose is. We've been studying this for the last, as I mentioned 15 years and we have a translational laboratory where we ask these very key questions. Whether the cells will work, where the cells are in the body.

What is the timing of when they should be injected. All these very important principles and concepts that need to be answered before you bring this type of innovation to a baby. We've been studying for 15 years and we know a lot about how stem cells work, especially in the in children. We've been funded by the NIH, the National Institute of Health. And we've been successful in carrying out multiple grants along these lines. We're very excited that now we have moved from the data that we collected with the preclinical studies, mostly in animals where we demonstrated the efficacy and the safety of these cells.

Now we are studying whether these cells are safe and feasible in babies. Now we've finished the phase one, which is where you try to answer those simple concepts of feasibility and safety. And what we determined was that when you do inject the cells, they are extremely safe for the baby, and it is feasible to inject the cells into the heart. We have demonstrated that after one year we see the success of these end points. And we're also seeing early signs of efficacy that the cells are actually working in trying to remodel the myocardium. Now, what we're doing is that we're now proceeding through the phase two study. The phase two study is where you try to understand whether the cells are efficacious, whether the cells actually work. And that is a very key question.

Host: All of this sounds amazing and groundbreaking. I've certainly never heard of anything like this before. Give us a sense of how unique this type of trial is.

Dr. Kaushal: This is one of the few trials in the country that are occurring in patients with congenital heart disease. We at Lurie Children's are the leaders in stem cell therapy in congenital heart disease patients. We're carrying out currently two different enrolling clinical trials, both are at a phase two level. And we're also starting another phase one study in dilated cardiomyopathy patients.

Host: You know, I have to say that it is so promising to hear all the research and the trials that are going on to improve outcomes for these heart conditions. And you know, another that I've heard about is hypoplastic left heart syndrome, or HLHS for short. Can you talk a little bit about this? How many kids are affected and help us understand the gravity of this condition?

Dr. Kaushal: So, what I work on is a hypoplastic left heart syndrome. This is a condition that carries a high mortality rate if it's not corrected. In fact, babies cannot live without a surgical intervention. There's roughly about a thousand babies that are born with hypoplastic left heart in the United States. The one-year survival rate is 75 to 80% with surgery. When you look at 10 years survival, it is about 50 to 60%. So, clearly these babies need some type of intervention in order to improve their outcomes. One of their main reasons why they don't do well, is that they have one ventricle that is pumping out systemically. The left ventricle is hypoplastic. So it doesn't contribute. The right ventricle is the one that is pumping out systemically and the right ventricle can pump out blood to the rest of the body at the beginning, but then what happens in the majority of patients, is that the right ventricle tires out and becomes dysfunctional.

When the right ventricle becomes dysfunctional, it is then when the babies don't do well. And sometimes they die. So, what we're trying to do is we're trying to introduce inject stem cells into the right heart, their only ventricle to see if these cells can remodel and make the myocardium contract better in order to prolong their outcomes.

Host: So, so far, we've talked a lot about the research and trials you've been involved in, but I also know that you're a prolific heart surgeon for babies and children. So, I'd love to learn a bit more about how you go about preparing for heart surgery with an infant or child.

Dr. Kaushal: Before you take a baby to the operating room, you have to have a diagnosis. Sometimes babies have a murmur, sometimes they have symptoms and when that is worked up, trying to determine what's wrong with the baby, is where the diagnosis is made. It is typically made with an echo which is a machine that we could put on top of the heart. And it can give you a diagnosis of what is happening to the heart. If that cannot reveal all the information, there's other studies that we do include a CT scans and MRI scans, which help to determine, what is the cause of the congenital heart disease or gives you more an anatomical definition that is needed.

Once we make a diagnosis, most of the babies can be treated medically. They do not need surgery. However, if there's a plumbing issue or some other issue, then they would need surgery. And at that time we would intervene with a surgical treatment. And every baby is different and we try to provide and tailor the surgery to the individual patient.

Host: So I wanted to move on and learn a bit more about your approach to pediatric heart surgery and how it differs from others. I know specifically that Lurie Children's is a premier place to have pediatric heart surgery, but maybe you can unpack why that is.

Dr. Kaushal: So here at Lurie Children's, we have a dedicated heart center team, which is made up cardiologists, nurses, respiratory therapists, cardiac surgeons, nurse practitioners. There's a big team of professionals that are working to provide the best care for patients with congenital heart disease. It is our approach that we want to give the best care. We have a very dedicated team that looks at every patient that comes to us and come up with a very thoughtful and methodical plan of treatment. That treatment could be medical, but then it can evolve into surgical intervention. Because we have a interactive and collaborative heart center, we're able to tailor and making sure that we provide the best treatment plans for our patient. Along with this individual plan that we map out for each patient, we have expertise here, which is very important to be a top children's hospital. We're able to provide the most innovative, cutting edge technology, treatment options, and surgical intervention for our babies.

Host: Yeah. You know, one of the things that you just touched on was the expertise and, you know, in doing a little prep for this conversation, I know that one of the things that you're an expert in is neonatal cardiac surgery. So we've obviously talked about the number of years that it's taken to get you where you are. But maybe tell us a little bit about the specific training you've had to do to become an expert in neonatal cardiac surgery. Like how many heart surgeries have you done? What else has gone into that?

Dr. Kaushal: neonatal cardiac surgery is a specialized field in congenital heart disease. It is very important to understand the anatomical issues and also the surgical technique that is needed to correct that disease. I have performed hundreds of neonatal cardiac surgeries.

Host: Yeah. And with those hundreds of surgeries comes a lot of experience. And I guess this kind of brings me to my next question. You know, you have been working, as you mentioned before for over 20 years in this field. So, I was wondering if you could tell us how pediatric heart procedures have advanced in the last 10-20 years and what you think the future holds.

Dr. Kaushal: So, when you look at the field of congenital heart surgery, we initially just wanted to make sure that we can try to correct a congenital heart defect. And we can cut and sew pretty well now, in the sense that we can correct both congenital heart diseases and give them a good outcome. In doing so now, we noticed that some of the babies may developed renal problems, neurological problems that may be associated with the corrective surgery that we did when the baby was very young. And so now we're looking at important ways of improving the quality of life for these congenital heart disease patients. What this means is that beyond the heart defect, how is the baby living life or the teenager with the congenital heart disease interacting with society.

Are they going to school? Are they learning a trade? Are they bringing up a family? All those very key questions. And I think that it really focuses back to that first surgery, where the surgical operating room can really change the progression and the outcomes for these babies beyond their heart condition.

So we're trying to look at how you can prevent renal problems or kidney problems. We're trying to understand how the brain can develop normally in some of these congenital heart defects and also other aspects of their existence, in order to make them the best patients for growing up as well as having the best outcomes.

Host: Well, Dr. Kaushal, this has been a fascinating conversation. Before we close, is there anything else that you'd like to share with our audience today?

Dr. Kaushal: No, I think you covered everything and it was nice to be part of this podcast and to share my experiences as well as expose people to congenital heart disease.

Host: Absolutely. Well, thank you so much for your time.

Dr. Kaushal: Sure. Thank you.

Host: Thanks for listening to Precision, Perspectives on Children's Surgery, the podcast from Lurie Children's Hospital. You can visit Luriechildren's.org/heartcenter for more information, or to make an appointment, or to get a second opinion. My name is Prakash Chandran. Thanks so much for listening and we'll talk next time.