“The typical signs and symptoms of heart failure are muscle weakness, shortness of breath, exercise intolerance — these are all symptoms these kids are experiencing already. Kids with DMD are usually wheelchair-bound by about 10 to 12 years old. So, when a child is confined to a wheelchair, you’re not going to notice that they’re becoming progressively more fatigued or if they have exercise intolerance. A lot of the tried-and-true symptoms of heart failure are not being detected.”

Current guidelines recommend that these patients begin receiving cardiac screening, care and regular surveillance at the time of diagnosis.

“But there’s definitely a shortcoming when comparing these recommendations to what’s actually happening in many of the clinics,” she said. “Despite information suggesting that cardiac disease progression may be modified through medical management such as cardiac medications, only a small percentage of these patients are receiving them. Data regarding the indications for using these advanced cardiac therapies are limited, so I hope that my research can help in this area.”

Witman’s groundbreaking research will dive into what is happening within the heart muscle as well as the arteries throughout the rest of the body in kids with DMD and BMD.

“The heart itself is problematic as it becomes weak and damaged due to the disease, but we also think that there’s something else going on downstream in the arteries causing resistance that inherently is also going to make the heart work harder to pump blood out. This is ultimately going to cause even more damage to the already failing heart.”

Medication, such as high-dose steroids, that children, particularly with DMD, are taking could also be causing cardiovascular impacts though they’re necessary to combat other symptoms of the disease.

“The steroids are very helpful in some aspects of the disease, but there are most likely some downstream effects that are occurring, particularly in the peripheral arteries. Children with BMD are not typically treated with these particular medications—so that could be an interesting comparison,” she said.

Research for this project, all happening on UD’s STAR Campus, will utilize innovative methodology. Using state-of-the-art methodology developed by Dr. Julio Chirinos, a cardiologist at the Perelman School of Medicine at the University of Pennsylvania, Witman will examine the pulsatile load on the heart or how hard the heart has to work to pump blood throughout the body.

“Through a combination of non-invasive measurements in the periphery as well as performing an echocardiogram, we can dissect the forward-moving and reflected pressure waves throughout the arterial system and assess how hard the heart is working, including any extra ‘wasted’ effort that could be causing further strain on an already damaged organ,” Witman said. “No one else is using this methodology to study these children, which makes this really exciting.”

The study will include three groups, including two patient groups consisting of 80 to 100 boys, ages 7 to 17, who have been diagnosed with DMD and BMD. A third group will include approximately 50 typically developing children. Children in each group will come in for measurements, including non-invasive tests to examine cardiovascular function and an echocardiogram.

“Further, the patients with Duchenne and Becker, we will ask to come back one and two years later—that’s the longitudinal component that will give us a better sense of cardiac disease progression in these children,” said Witman.

Children with DMD and BMD will be recruited from the surrounding area through a collaboration with Dr. Mena Scavina, a pediatric neurologist at Nemours Children’s Hospital, Delaware, as well as from Children’s Hospital of Philadelphia and the Kennedy Krieger Institute at Johns Hopkins in Baltimore, Maryland. 

Ultimately, the long-term goal of this research is to reduce not only the incidence of heart disease, but also delay the progression so that, hopefully, these children suffer less and live longer.

Even with her research potentially leading to major advances in fighting cardiovascular disease in patients with muscular dystrophy, Witman isn’t certain doctors and scientists will ever be able to eliminate all heart disease in these children. But she hopes that future therapeutic approaches will target the heart specifically.

“These are tragic, and currently, incurable diseases, and so ultimately, I would like to improve not only life expectancy but also quality of life. Currently, many of the new drugs being developed, including various gene therapies, are still primarily focused on the skeletal muscle. However, as we begin to understand more about the DMD- and BMD-induced cardiovascular complications, I hope that changes,” Witman said. “Our work will help to inform future interventional studies, including potentially, clinical trials that would then have a direct effect on altering the trajectory of care for these patients.”