Duchenne muscular dystrophy is the most common and severe form of muscular dystrophy. According to Nemours KidsHealth.org, it affects boys more often than girls. According to the Muscular Dystrophy Association, heart and respiratory muscle problems emerge in the teen years and can lead to serious complications. In terms of the heart, the issue at hand is cardiomyopathy. Dr. Takeshi Tsuda is a pediatric cardiologist at Nemours Children’s Health who studies cardiomyopathy in boys with Duchenne. He joins this episode to talk about the unique qualities of cardiomyopathy in young teenagers with Duchenne muscular dystrophy, which have not previously been well characterized.
Guests:
Takeshi Tsuda, MD, Pediatric Cardiology, Nemours Children’s Health, Delaware Valley
Producer, Host: Carol Vassar
EPISODE 59 TRANSCRIPT
Carol Vassar, podcast host/producer:
Welcome to Well Beyond Medicine, the Nemours Children’s Health Podcast. Each week, we’ll explore anything and everything related to the 80% of child health impacts that occur outside the doctor’s office. I’m your host, Carol Vassar, and now that you are here, let’s go.
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Let’s go well beyond medicine.
Carol Vassar, podcast host/producer:
Duchenne muscular dystrophy is the most common and most severe form of muscular dystrophy. According to KidsHealth.org, it affects boys more often than girls. Symptoms usually emerge between the ages of three and five and can include falling, having trouble going upstairs, running slowly, and toe walking. By age 12, most of the boys affected are using a wheelchair. Heart and respiratory muscle problems emerge in the teen years and can lead to serious complications, according to the Muscular Dystrophy Association. In terms of the heart, the issue at hand is cardiomyopathy.
Dr. Takeshi Tsuda is a Nemours pediatric cardiologist who studies cardiomyopathy in Duchenne boys. He sat down with me to explain cardiomyopathy in general and the unique qualities of cardiomyopathy in young teenagers with Duchenne muscular dystrophy, which have not previously been well characterized. Here is Dr. Takeshi Tsuda.
Dr. Takeshi Tsuda, Nemours Children’s Health:
Regular cardiomyopathy, which start with some cell death due to any intrinsic genetic condition or environmental condition, which is a marker that is drug-induced, whatever, because of that initial impairment of the cell, kill the cells. And as a result, contractility goes down. Once that contractility goes down, the natural response to that decreased contractility increase the preload, which just makes the heart big. So at the result, the heart muscle become what we call hypertrophy, or enlarged, so make the heart bigger. And once that vitriol cycle continues to progress, it cause what we call dilated phenotype, the cause of dilated cardiomyopathy. So it’s a big, dysfunctional heart, and that’s dilated cardiomyopathy.
Now, in Duchenne muscle dystrophy, that’s not the case. Now, when we are looking at our study patients, the first of all, the heart size never get enlarged. It’s basically the normal size, actually smaller size. At the same time, high incidence of myocardial fibrosis before the dysfunction happens. The mechanism of the disease progressions is not the same as the other known cardiomyopathy.
And that’s why we prove in our study, basically show, A, that we group the patient into three groups based upon the age: one is less than 10 years old, 10 to 15 years old, above 15 years old. And looking at MRI results, the size of the ventricle and also size of the myocardial mass, so muscle mass, they’re actually very low at the beginning and get lower in the second age, which is age 10 to 15, it’s less than average. And above the age of 15, some start to become a dilated feature. And probably once you get older, like 20s or 30s, that dilatation continues to progress. So at the end stage, we may be seeing the dilated cardiomyopathy, but what we’re seeing in the pediatric age is not the dilated cardiomyopathy.
So what happened was that cells are very vulnerable to stress and the heart is beating 100,000 times per day against your blood pressure, it’s a lot of stress happens on the myocardial cells, and that induces the cell death. And dystrophin not only support that function, but also serve a mechanical sensor. Mechanical sensor is something that when you stretch, that stretch enhance the signaling to get hypertrophy. That’s a natural response. Any cardio muscle cell, that’s a known mechanism. But because mechanical sensor function is lacking, they cannot really get enlarged, hypertrophy.
And also, once the cell dies, the cell is gone, so something have to replace that open space. That’s fibroblast. Fibroblast is coming into that open space and secrete collagen to make what we call fibrosis. And as a result of fibrosis, cell-cell connection, we call cell adhesion, that becomes different, so it’s become more slippery. So once the fibrosis become advanced, then finally, dilatation is going to happen.
So it’s not exactly different, but what we are seeing at the early stage, pediatric stage, is really cell death and an atrophic heart. So really, muscle mass is declining in the heart. Just as skeletal muscle, your heart muscle is kind of getting thinner. And after that, it started dilated as a result of fibrosis. And when we look at the fibrosis, fibrosis usually suggests advanced stage of cardiomyopathy. However, when we look at Duchenne patient in three different groups, the incidence of fibrosis is about the same regardless of age, regardless of ventricular function. We found that the incidence of fibrosis is about 70% in less than 10 years old regardless, and their heart is almost always look good. But in fact, incidence of fibrosis, already 70% of those patients, that persists. Once they get to more than age 15, a little bit increase in incidence, 80%. So fibrosis is not the sign of the advanced stage. It happens from get-go with atrophic heart. Eventually, once the environmental change, then a patient have as a secondary phenomenon, which is beyond the pediatric age group. So those are mechanisms of difference.
So one thing we learned is that when we initially, like 10 years ago, when the ventricle is working fine with the echocardiogram, we thought this fine. However, what we learned is that even with a younger stage, disease already started. It’s just a matter of you don’t see it, doesn’t mean it doesn’t exist. So we have to change our own thought that because that progressive mechanism of cardiomyopathy much different in Duchenne muscular dystrophy, we need to understand that earlier treatment is essential for these patients regardless of echo finding. That’s-
Carol Vassar, podcast host/producer:
So early intervention, is that helpful?
Dr. Takeshi Tsuda, Nemours Children’s Health:
Yeah. So there are several anecdotal retrospective study published, and it said that to some extent, yes, it delays a progression. And that also is shown in animal studies. Now, all depends upon what marker you use, meaning that ventricular function of the heart, patient survival, patient quality of life, all three are different things. This is a condition that’s very hard to do a clinical trial because they are all equally suffered from this condition. And it’s really hard to say that I’m going to give you this for you, but not to you. Ethically, it’s quite challenging. I think that most of the clinical study of Duchenne muscular dystrophy patient is really anecdotal experience, and in some people that it’s worked, yes, that it works.
Carol Vassar, podcast host/producer:
Dr. Takeshi Tsuda is a pediatric cardiologist with Nemours Children’s Health, Delaware.
MUSIC:
Well beyond medicine!
Carol Vassar, podcast host/producer:
Thanks for joining us on this mini episode of the Nemours Well Beyond Medicine Podcast. Our production team for this episode is Che Parker, Susan Masucci, Lauren Teta, and Cheryl Munn. Thanks to Dr. Tsuda for sharing his expertise and thank you for listening. You can find all of our podcast episodes at nemourswellbeyond.org. That’s nemourswellbeyond.org.
I’m Carol Vassar. Join us next time as we talk with Black leaders from across Nemours Children’s Health to honor and celebrate Black History Month. Until then, remember, we can change children’s health for good well beyond medicine.
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Let’s go well beyond medicine.
