Intro: Welcome to Pediatric Voices, Duke Children's podcast about kids' healthcare. Now, here's our host, Dr. Angelo Milazzo.

Angelo Milazzo, MD (Host): Hello and welcome to Pediatric Voices, a podcast that dives deeply into conversation with the people who make up the Duke Children's Healthcare team, to learn about who they are and what they do. I'm Dr. Angelo Milazzo, a Pediatric Cardiologist and Professor of Pediatrics at Duke Children's, and a co-host of the podcast. My friend and colleague is Dr. Richard Chung. Richard is a Pediatric and Adolescent Medicine Specialist, and a Professor of Pediatrics at Duke Children's. You'll meet Richard in upcoming episodes. We're both looking forward to bringing you expert insights about timely topics in children's health. On this episode of Pediatric Voices, we'll look at the topic of Cardiovascular Genetics, and specifically we'll try to answer a really important question, the question of when parents should worry about passing down a heart condition to their children.

In the last decade or so, our understanding of the human genome and genetic diseases has exploded. There've been exciting new genetic technologies and we seem to be at the dawn of an era of developing some very specific treatments and potentially even cures for some genetic conditions. Genetic technology is in the news seemingly every day. People are getting Nobel prizes for discoveries in genetics. Words like CRISPR are becoming part of the common lexicon of everyday news. And, it's just a really interesting and exciting time to be talking about this subject.

So, to help us understand this better, let's talk to Dr. Andrew Landstrom, a Physician and Faculty Member here at Duke Children's. Dr.Landstrom is a Pediatric Cardiologist. In other words, a pediatrician who specializes in cardiac conditions. He's a Pediatric Electrophysiologist. In other words, a pediatric cardiologist who specializes in diseases which affect the electrical conduction system of the heart.

And on top of all that, he's a Pediatric Cardiovascular Geneticist. In other words, he studies the genetic basis of the cardiac conditions which impact children. Dr. Landstrom is an Associate Professor of Pediatrics in the Duke University School of Medicine, and he holds faculty appointments in several programs here at Duke, including pediatric cardiology, stem cell biology, molecular biology, and genetics.

He directs the Duke Pediatric Research Scholars Program for Physician Scientist Development and he does many, many other things. Too many to list here. Welcome, Andrew. It's a tremendous pleasure to have you on Pediatric Voices. How does it feel to be the inaugural guest on our inaugural episode?

Andrew Landstrom, MD, PhD: Oh, Angelo, thank you very much. It feels wonderful. A pleasure to be here.

Host: Excellent. So, Andrew, let's start sort of at the beginning, your origin story, so to speak. How did you get interested and involved in the care of children?

Andrew Landstrom, MD, PhD: Thank you and, and again, pleasure to be here. You know, kind of, as far back as I can remember, I've always kind of been a bit of a nerd, that kid who loved science and loved reading and kind of sat in the back of the classroom and just daydreamed about ways science might come to fruition, to help people.

And for me personally, it's always been sort of a calling. I absolutely love the idea of human genetics, of how genetics can be leveraged to help people. When I was in high school, I remember very distinctly, the human genome being sequenced for the first time. And we know now that that sequence had a lot of holes in it. It was only in a couple of individuals. But that really kind of planted this seed in my head about the power of genetics. And if one could understand the genetic underpinnings of what makes us healthy and what makes us sick; one might be able to figure out who is at risk of developing disease before disease occurs.

And one might be able to fix that disease at the genetic level before disease occurs. And so that was always very exciting for me. I went to graduate school to learn more about how genetics can be leveraged to help people and in medical school as well, to learn about the practice and the art of medicine.

As you nicely indicated, that kind of led me to pediatric cardiology, which I think is really the perfect field for me because it allows me to care for children, adolescents, young adults, who have these cardiac diseases. Oftentimes the thread between all of these patients is that their diseases can be passed in the family, so-called genetic diseases, heritable diseases. So that's really been my passion and I absolutely love every day coming to work.

Host: Tell us a little bit about that work, Andrew, from a day-to-day perspective. Talk a little bit about the kinds of patients you're seeing, the kinds of problems and the types of evaluations and treatments that you're able to offer to those patients.

Andrew Landstrom, MD, PhD: I like to think I get to do two things every day that I absolutely love. The first is patient care. And so, we run a Cardiovascular Genetics Clinic here at Duke Children's. It's based out of the main Duke Children's, Children's Health Center here in Durham. And we try to provide expert care through a multidisciplinary team for children, young adults, and families with heritable cardiac conditions, disease they can pass down from parent to child.

The common thread for a lot of these diseases is they can cause the heart to arrest, go into a big heart attack, potentially at a young age, and sometimes in tragic cases cause sudden cardiac arrest and sometimes death. And so these patients require a lot of expert knowledge to make sure we get their disease diagnosis right, that we come up with an individualized personalized care strategy to be able to treat their disease effectively and to balance the risk associated with this disease, with allowing those kids to get back to being kids and playing sports and living lives and those kinds of things. The second thing I get to do every day is research.

And so, you can't see cause this is a podcast, but back behind the wall of my office, on the other side of that wall, is a wet lab. And in that wet lab, we study the way in which these genetic diseases develop. And the overall reason for wanting to do that, is so that we can come up with new therapies, to leverage the knowledge that we can learn from the genetic causes of disease, to make new medications. And you're absolutely right. There is a lot of really incredible advancement that's been in this field in the past few years. And one of the things we're trying to leverage is new therapies that take advantage of those new breakthroughs. And one of them that's really exciting that we may be able to talk about a bit later is gene therapy.

And so by doing these two things every day, I hope that I can identify patients who are at risk and cure their disease and someday put myself out of business.

Host: You're not over exaggerating when you talk about the exciting things that are happening. And one thing that occurs to me, Andrew, is what we've seen in the last few years is genetic technology has made its way into the commercial space. You know, today a family can purchase a testing kit, a commercially available kit, from any number of large retailers that we're all familiar with. They can have a shipped to their home, they can do a simple saliva test and send that kit back and get information. How has that availability of that kind of testing impacted your work and what is your perspective on that kind of availability of the technology?

Andrew Landstrom, MD, PhD: I really think of this kind of testing sometimes called at home gene testing or direct to consumer gene testing in sort of two different baskets. The first basket, is ancestry. And so there's a lot of gene testing companies that will say, we'll look at your DNA and give you an idea of your ancestry that's built into your DNA, whether you are of African descent or Northern European descent, or, Asian descent.

 I have lots of different ancestries in my background and so have done these at home ancestry tests and really find the results fascinating. And then there's the other kind of at home gene testing and like you were saying, it can be a little bit more complex. You can send off your own DNA sample right now and have your genome sequenced. You can send off a DNA sample and figure out if you've got these misspellings in the DNA called genetic variants that might be associated with any number of health conditions. But these are very challenging. Oftentimes the science that backs up a lot of these associations, can be variable.

So some genetic research is really, really strong in one area, but in another area that research may not be as strong. And the gene test oftentimes is hard to interpret because you don't know when you get the results back how much or how little should I be worried? How good or how bad was the science that was behind this test result? And then what do I do with it? And so that sort of diagnostic gene testing at home where it's trying to predict who's going to get disease before it happens, is much more complex. I would recommend if families are considering doing this, to talk with a doctor first about what those results might mean before the results ever come back, because it may uncover a lot of questions in the minds of the family, in the minds of the people getting the gene testing that weren't considered. And certainly if those results come back concerning, then that would be a great time to talk to a specialist. Not just anyone, but a specialist in genetics, in particular, in that field of whatever the disease is that was found, or whatever that association was that caused a little bit of a concern. Talk with a specialist and have them help you take the next best steps.

Host: Andrew, I want to underline this because I made a promise at the beginning of the show that we would address this for our listeners. So, if a family is worried, if they're concerned that there may be a genetic condition in the family, specifically one that could impact the cardiac health of their children, how would you outline their first steps?

Andrew Landstrom, MD, PhD: We see this very frequently in our clinic. Oftentimes there's been a disease that's been diagnosed in one, sometimes both of the parents. And the question becomes well, this disease can be heritable, meaning biological children of that mother or father would be at risk of developing that same disease. And so often we say, if that's a concern, then come see us in clinic. Because oftentimes the next best test is not the genetic test. The next best test is to figure out what that disease was in the parents. And so we work closely with the adult providers who raised concern about that genetic disease to make sure that yes, we agree that there is a diagnosis in that parent that might be conveying risk to the children.

And then we turn to the child or the young adult who's in our clinic, and oftentimes the next best test is not genetic for that family. Oftentimes, the next best test is good old fashioned medicine. We start with a history and a physical exam, and that history delves into things like does your child have red flags? So from a heart perspective, I always worry about fainting with exercise or fainting right after exercise or right after sports participation or during sports participation as one example of a red flag. We ask a lot about the family. I want to know about the parents because they were the ones with the concern for the gene testing first.

But I want to know about their siblings, their biological parents, grandma and grandpa and I want to know about the siblings of the patient in front of us. Very important to figure out if any of them have any of those red flags, any other diagnoses, and oftentimes we'll ask for their records, if the family gives us permission, of course, so we can learn more about what cardiac disease they may or sometimes may not actually have.

And then the next best test isn't actually genetic. It's oftentimes our routine cardiac testing that we would do for any number of patients. We can look at the electricity of heart with an electrocardiogram, we can look at the structure and the strength of the squeeze of the heart with an echocardiogram and testing like this really kind of adds to an overall picture of the family and of the child in front of us that we then step back from and say, is now genetic testing the right choice for this family?

Host: So Andrew, would you recommend in those cases, if there is such a concern and this type of evaluation sounds appealing to a family, should they discuss it with their primary care physician first? Should they contact you or one of your colleagues directly? What do you recommend as a first foray into the evaluation?

Andrew Landstrom, MD, PhD: I think it depends a little bit on what the concern is. I always think a great place to start is your general pediatrician, your general family practice provider. Your family's primary care home is always a great resource for you as a initial platform for someone to kind of address your concerns if you have them.

Certainly if there's history of cardiac disease that is known to be heritable, some of these diagnoses are things like hypertrophic cardiomyopathy. It's a very common cardiovascular, genetic disease, thickening of the heart. Sometimes electrical diseases like long QT syndrome, can be a heritable disease. And so if that diagnosis is already known and there's more focused questions, perhaps about the heart and what that may mean for children or other members of the family; then yes, our clinic would be well positioned to be able to provide that support in addition to the cardiologist who helped to raise the concern for the family.

And if that cardiologist feels like this is getting into something that they're a little bit less comfortable with, because all of these diseases can be rare diseases even in the cardiac space, then we and other cardiovascular genetic centers are here to provide some backup support, some consultation, some teamwork to be able to make sure that your family gets the care that they need.

Host: I really like the thoughtfulness of that approach. I really like the supportive feel. It sounds like families should, if they have any reticence about it, they should really put those fears aside and reach out, as you say, perhaps starting with their primary care provider, perhaps communicating directly with you and your team.

It sounds like there are multiple options and in either case, they're, they're going to get a fantastic evaluation and it's going to be provided in a way that feels very supportive, very engaging, very transparent, and in a way that will educate the family during the process. So that sounds wonderful.

Let's talk a little bit about what's on the vanguard. What do you see on the horizon and what's in the future? What's the most exciting potential future development, in your field? What's should our listeners know about what's ahead?

Andrew Landstrom, MD, PhD: It is an incredible time. These diseases, as you can imagine, can be scary. When we talk about things like heart attacks and sudden cardiac arrest in children and young adults; that can be very upsetting. We have great therapies now that we can greatly diminish the risk of those things, whether they're medications or even some surgeries that are very specialized that can lower that risk.

But we are at a truly incredible time. You mentioned some of them in the introduction, things like CRISPR/Cas 9 and gene editing strategies. It used to be that things like gene therapy back in the nineties was really not considered anything that could reach prime time, that was ready for patient care broadly. That's really changed. There are clinical trials now. We help to inform those clinical trials for many of these syndromes based on our research about how can you actually leverage safe gene therapy to be able to treat these diseases, lower the risk of really terrible side effects of the disease process, whether it's fainting or seizure-like activity or not being able to do sports, or even preventing or lowering the risk of sudden cardiac arrest.

I think in the next five to 10 years we're going to see more and more of these gene trials make it through the FDA approval process. There are many families with these genetic syndromes that want this process to be much faster, as you can imagine. Unfortunately, there is a time table that's set up by the FDA and the reason behind that is, that safety's front of mind.

So this may take five to 10 to 15 years to reach our clinic for most of our patients. But that's mainly because we want to make sure these therapies are safe and that when you are getting a gene therapy that you understand what those risks are. That we know that those risks are less than the benefits that the gene therapy provides and that we know what to expect.

 And so that just takes time. But I think in my lifetime, certainly, the field is going to transform into one of reaction. So there is a disease in the family, or maybe even a terrible tragedy in the family. And we react to it by diagnosing the family and treating others with disease to one of prevention where we're able to spot the disease before it happens and treat it before those individuals have some of the terrible outcomes that these diseases can have.

Host: That's amazing. You know, we talk all the time in our circles about taking what happens in the laboratory or in what we call the basic science and translating it into the actual clinical care of patients. And this sounds, to me, like a tremendous example of that type of achievement. So I agree with you. The level of excitement is high. We're all interested to see where this is headed. I want to ask you a few questions about, Andrew Landstrom, the person. Andrew, what inspires you? It sounds like you are extraordinarily passionate about your patients and the kinds of care options that you can provide for them and some of the therapeutics that are coming down the line. What really gets you up and into the office every day and what's pushing you toward these amazing achievements in patient care?

Andrew Landstrom, MD, PhD: I get to come in every day and work with incredible patients, incredible families, and incredible colleagues. Many of these diseases that we treat in our clinic are quite rare. They can be quite serious, but when you work closely with a family and you understand what their goals are, what their fears are; you leverage the best science, the best evidence to be able to help them with their disease. And you can see that you're lowering their risk of those terrible side effects and then you get them back to being kids, right? Sports can sometimes bring out bad side effects with a lot of these diseases.

And to see an athlete who's been benched because of concern for these diseases, to diagnose them, to identify what their risk is, and then through that personalized strategy, lower their risk and get them back on the field and then get to see them do incredible things; is why I think we all get into this business. They're the people who get me up in the morning, get me coming in every day and give me promise that we can actually cure these diseases down the road if the science can meet the moment.

Host: And if you hadn't found your calling as a pediatric cardiologist and electrophysiologist and geneticist, if that hadn't been your path, who would you be? What would you do?

Andrew Landstrom, MD, PhD: Well, it is hard for me to imagine anything outside of science or medicine. But, I've always had a love of photography. I'm a terrible photographer, but I love, photography and I probably would try to do something in that space. Photojournalism sounds really appealing. Again, a terrible photographer technically, so I'd have to kind of address that. But maybe if this doesn't work out, there's another career for me somewhere there.

Host: Fair enough. I have no doubt you would be talented, and very successful in whatever field you chose. Andrew, let's take you out with this question. As our listeners are digesting our conversation today and sorting through some of the topics that we've touched on, if they want to take action, we've talked a little bit about what they might do, but what words would you leave them with if they have remaining questions, if they're seeking answers, if they have concerns. What should our listeners take home as their message today as advice from Dr. Andrew Landstrom?

Andrew Landstrom, MD, PhD: If you have worries or concerns for any of these diseases, you're not alone. We are here to help, your physicians who care for your family already are here to help as well. We're here to partner with them to get you the best care that you need and oftentimes there's this misconception that diagnosis with a significant heart condition prevents you from living your life or lives of your children if they're en engaged in sports and those kinds of things. But our goal is not just to lower the risk of disease overall and to keep you healthy, but it's to keep you healthy so that you can do what you love. Your kids can keep doing the things that make them them, and we're here to help, if you need us.

Host: Well, Andrew, that was fantastic. It was such a pleasure to have you. I want to thank my guest, Dr. Andrew Landstrom for his participation in today's podcast and also thank him for being such a great partner in practice. He has helped so many of my own patients and their families, and I am personally very grateful for being able to work with a colleague like Dr. Landstrom and to have him participate in the care of my own patients. So, thank you so much for being with us today, Andrew.

Andrew Landstrom, MD, PhD: It's my pleasure. Thank you for having me.

Host: Well, thank you to our audience for being a part of the show. Pediatric Voices is brought to you by Duke Children's Hospital and the Department of Pediatrics at the Duke University Medical Center in beautiful Durham, North Carolina. Pediatric Voices was created by my friend, Dr. Richard Chung, and by me, Dr. Angelo Milazzo. Rebecca Casey provided a huge assist. Our podcast is produced by Dr. Podcasting. Thanks to Dr. Ann Reed and the team at Duke Children's for their support. You can find our podcast and hit the subscribe button wherever you find your favorites, Apple Podcasts, Google Podcasts, Stitcher, TuneIn, iHeartRadio, and Spotify.

We want to hear from you, so connect with us at dukechildren's.org, at Facebook /Duke Children's and at Twitter /Duke_Children's. Like I said, we'd love to hear from you, so please leave us a review. Thanks for being part of the show. We'll see you next time.