Wayne Franklin, M.D., F.A.C.C.

Wayne J. Franklin, M.D., F.A.C.C., named senior vice president of Children’s National Heart Center

Wayne Franklin, M.D., F.A.C.C.

Dr. Franklin will oversee the full spectrum of heart care services including cardiac imaging and diagnostics, interventional cardiology, electrophysiology, cardiac anesthesia, cardiac surgery and cardiac intensive care.

Children’s National Hospital has appointed Wayne J. Franklin, M.D., F.A.C.C., as the new senior vice president (SVP) of the Children’s National Heart Center. In this role, Dr. Franklin will oversee the full spectrum of heart care services including cardiac imaging and diagnostics, interventional cardiology, electrophysiology, cardiac anesthesia, cardiac surgery and cardiac intensive care. He joins us from Phoenix Children’s in Arizona and starts June 2024.

Dr. Franklin currently serves as co-director, medical director of Quality and endowed chair in the Center for Heart Care and associate director of the Adult Congenital Heart Disease Program at Phoenix Children’s. He’s also a professor of Child Health, Medicine, and Obstetrics and Gynecology at the University of Arizona College of Medicine – Phoenix.

Dr. Franklin is involved with research focused on adults with congenital heart disease, specifically single ventricle-Fontan physiology, neurocognitive outcomes, pulmonary hypertension, cardiac disease in pregnancy and transition medicine. After a national search, he stood out for his clinical and research accomplishments, as well as his demonstrated ability as a visionary leader and mentor.

“I look forward to leading the exceptional Heart Center team at Children’s National, as we contribute to advancing pediatric cardiac care and research,” said Dr. Franklin. “There is a clear dedication to clinical excellence and innovation, and together we’ll continue to advance the field and make a lasting impact on the lives of the children and families we serve.”

Dr. Franklin is a graduate of Williams College in Williamstown, MA, and UCLA School of Medicine. He completed his residency training in internal medicine and pediatrics at Duke University. He then completed two simultaneous fellowships in adult cardiology and pediatric cardiology at St. Luke’s/Texas Heart Institute and at Baylor College of Medicine/Texas Children’s Hospital in Houston.

“Dr. Franklin brings a wealth of expertise and steadfast leadership that will undoubtedly strengthen the foundation of our cardiac program,” said David Wessel, M.D., executive vice president, chief medical officer and physician-in-chief at Children’s National. “Together with our Heart Center leadership team, he will ensure we’re meeting the highest standards of safety, quality and innovative care for our patients and families.”

The Children’s National Heart Center is a multidisciplinary center that provides high-quality and innovative pediatric cardiac care. In his role as SVP, Dr. Franklin will lead our Heart Center to new heights in pediatric heart care, innovation and education, working together with Yves d’Udekem, M.D., Ph.D., chief of the Division of Cardiac Surgery, Ricardo Muñoz, M.D., chief of the Division of Cardiac Critical Care Medicine and Andrew Waberski, M.D., director of Pediatric Cardiac Anesthesia.

Bloom Standard 2 Portable UltraSound Device being used on a baby

Novel ultrasound device gets FDA breakthrough designation with Children’s National support

The Bloom Standard device enables autonomous, hands-free ultrasound scans to be performed anywhere, by any user.

A novel ultrasound device developed by Bloom Standard received the Food and Drug Administration’s valued  breakthrough device designation with the help of Children’s National Hospital and support provided through an  FDA-funded grant that established the Alliance for Pediatric Device Innovation (APDI), formerly branded as the National Capital Consortium for Pediatric Device Innovation (NCC-PDI). The grant funding, clinical expertise and regulatory guidance demonstrate the hospital’s leadership in pediatric medical device innovation and its commitment to supporting critically needed advancements.

“In many ways, Children’s National has been a key resource as we continue this journey from concept to commercialization,” said Annamarie Saarinen, co-founder of Bloom Standard and the mother of an infant who was diagnosed with a critical heart defect days after her birth.

Why we’re excited

Children’s National Innovation Ventures and APDI leaders saw the value in the Bloom Standard innovation: a device that enables autonomous, hands-free ultrasound scans to be performed anywhere, by any user. The FDA granted the innovation its breakthrough device designation to help streamline the regulatory process so that patients and healthcare providers have more timely access to devices.

Bloom Standard can potentially save lives and improve outcomes for newborns and babies with cardiac and respiratory issues. The technology can eliminate the delay that often occurs for infants who need ultrasound imaging because their medical location lacks the technology. Bloom Standard’s portability and ease of use can potentially reduce mortality and poor outcomes tied to delayed detection of lung and cardiac conditions. It has potential cost savings, too.

Children’s National leads the way

Children’s National supported this novel medical technology for children by engaging in multiple steps through the regulatory process:

  • Grant funding: Bloom Standard participated in pediatric pitch competitions in 2020 and 2022 and each time, because of the merits of the device, was awarded grant funding that helped to support its progression.
  • Regulatory support: Children’s National pediatrician Francesca Joseph, M.D., brings a wealth of expertise navigating the FDA’s regulatory processes and currently service as co-investigator and core regulatory expert for the pediatric device consortium led by Children’s National. Saarinen called Dr. Joseph “an invaluable resource,” explaining that her input and support has been very significant in Bloom Standard’s understanding and navigation of FDA processes. “For a small device company like ours, she has been a lifeline,” Saarinen said.

Saarinen says she is grateful for the continuing relationship with Children’s National as her company enters its next phase on the journey to commercialization.

Children’s National Vice President and Chief Innovation Officer Kolaleh Eskandanian, Ph.D., MBA, PMP, who directs the FDA-funded Alliance for Pediatric Device Development, says that nurturing and supporting life-saving technologies like Bloom Standard is important because the device addresses a dire unmet need in the pediatric space, especially in settings with fewer resources and in public health emergency situations. “Advancements in children’s medical devices continue to lag behind those of adults, and we must use our research and innovation infrastructure to help close that gap and to influence policy changes.”

Newborn baby in a crib

Pioneering research center aims to revolutionize prenatal and neonatal health

Catherine Limperopoulos, Ph.D., was drawn to understanding the developing brain, examining how early adverse environments for a mother can impact the baby at birth and extend throughout its entire lifetime. She has widened her lens – and expanded her team – to create the new Center for Prenatal, Neonatal & Maternal Health Research at Children’s National Hospital.

“Despite the obvious connection between mothers and babies, we know that conventional medicine often addresses the two beings separately. We want to change that,” said Dr. Limperopoulos, who also directs the Developing Brain Institute. “Given the current trajectory of medicine toward precision care and advanced imaging, we thought this was the right moment to channel our talent and resources into understanding this delicate and highly dynamic relationship.”

Moving the field forward

Since its establishment in July 2023, the new research center has gained recognition through high-impact scientific publications, featuring noteworthy studies exploring the early phases of human development.

Dr. Limperopoulos has been at the forefront of groundbreaking research, directing attention to the consequences of maternal stress on the unborn baby and the placenta. In addition, under the guidance of Kevin Cook, Ph.D., investigators published a pivotal study on the correlation between pain experienced by premature infants in the Neonatal Intensive Care Unit and the associated risks of autism and developmental delays.

Another area of research has focused on understanding the impact of congenital heart disease (CHD) on prenatal brain development, given the altered blood flow to the brain caused by these conditions during this period of rapid development. Led by Josepheen De Asis-Cruz, M.D., Ph.D., a research team uncovered variations in the functional connectivity of the brains of infants with CHD. In parallel, Nickie Andescavage, M.D., and her team employed advanced imaging techniques to identify potential biomarkers in infants with CHD, holding promise for guiding improved diagnostics and postnatal care. Separately, she is investigating the impact of COVID-19 on fetal brain development.

In the months ahead, the team plans to concentrate its efforts on these areas and several others, including the impact of infectious disease, social determinants of health and protecting developing brains from the negative impacts of maternal stress, pre-eclampsia and other conditions prevalent among expectant mothers.

Assembling a team

Given its robust research plan and opportunities for collaboration, the center pulled together expertise from across the hospital’s faculty and has attracted new talent from across the country, including several prominent faculty members:

  • Daniel Licht, M.D., has joined Children’s National to build a noninvasive optical device research group to better care for children with CHD. Dr. Licht brings decades of experience in pediatric neurology, psychiatry and critical care and is recognized internationally for his expertise in neurodevelopmental outcomes in babies with CHD.
  • Katherine L. Wisner, M.S., M.D., has accumulated extensive knowledge on the impact of maternal stress on babies throughout her career, and her deep background in psychiatry made her a natural addition to the center. While Dr. Wisner conducts research into the urgent need to prioritize maternal mental health, she will also be treating mothers as part of the DC Mother-Baby Wellness Initiative — a novel program based at Children’s National that allows mothers to more seamlessly get care for themselves and participate in mother-infant play groups timed to align with their clinical appointments.
  • Catherine J. Stoodley, B.S., M.S., D.Phil., brings extensive research into the role of the cerebellum in cognitive development. Dr. Stoodley uses clinical studies, neuroimaging, neuromodulation and behavioral testing to investigate the functional anatomy of the part of the brain responsible for cognition.
  • Katherine M. Ottolini, M.D., attending neonatologist, is developing NICU THRIVE – a research program studying the effects of tailored nutrition on the developing newborn brain, including the impact of fortifying human milk with protein, fat and carbohydrates. With a grant from the Gerber Foundation, Dr. Ottolini is working to understand how personalized fortification for high-risk babies could help them grow.

Early accolades

The new center brings together award-winning talent. This includes Yao Wu, Ph.D., who recently earned the American Heart Association’s Outstanding Research in Pediatric Cardiology award for her groundbreaking work in CHD, particularly for her research on the role of altered placental function and neurodevelopmental outcomes in toddlers with CHD. Dr. Wu became the third Children’s National faculty member to earn the distinction, joining an honor roll that includes Dr. Limperopoulos and David Wessel, M.D., executive vice president and chief medical officer.

Interim Chief Academic Officer Catherine Bollard, M.D., M.B.Ch.B., said the cross-disciplinary collaboration now underway at the new center has the potential to make a dramatic impact on the field of neonatology and early child development. “This group epitomizes the Team Science approach that we work tirelessly to foster at Children’s National,” Dr. Bollard said. “Given their energetic start, we know these scientists and physicians are poised to tackle some of the toughest questions in maternal-fetal medicine and beyond, which will improve outcomes for our most fragile patients.”

Daniel J. Licht, M.D.

Q&A with Daniel J. Licht, M.D.: The future of medicine is in light

Daniel J. Licht, M.D.

A pediatric neurologist who specializes in children with congenital heart disease, Dr. Licht initially came to this area of research as he considered ways to ensure children’s brains have adequate oxygen delivery during heart care, preserving neurological health and improving long-term outcomes.

Daniel J. Licht, M.D., joins Children’s National Hospital with a vision: He believes non-invasive devices built using biomedical optics – or instruments using light – can give clinicians invaluable information about how the brain and other organs are functioning.

A pediatric neurologist who specializes in children with congenital heart disease, Dr. Licht initially came to this area of research as he considered ways to ensure children’s brains have adequate oxygen delivery during heart care, preserving neurological health and improving long-term outcomes. He sees countless applications for using the properties of light in pediatric medicine.

Dr. Licht, whose name coincidentally also means “light” in German, is planning to establish a program for biomedical optics at Children’s National, built on the pillars of education, innovation and commercialization. He wants to tap into the resources of the Sheik Zayed Institute of Pediatric Surgical Innovation and expertise across the hospital. He is launching this effort as part of the new Center for Prenatal, Neonatal & Maternal Health Research.

Q: How can light be used diagnostically?

A: I believe that light is truly the future of biomedical devices, especially in children. Light can penetrate human tissues deeply, whether it’s muscle, liver or kidney. For example, you can put a light at the end of an endoscope and someday do virtual biopsies. It’s all a matter of understanding the properties of light, and how to manipulate light to give you the answers that you need. The applications are truly infinite.

Q: What has your initial work in neurology shown?

A: One of the instruments that we have developed can measure cerebral blood flow and quantitatively show the oxygen use of the brain. That’s important because it’s easy to measure oxygen delivery, but it’s hard to balance supply-and-demand without knowing the patient’s unique demand. We now have preclinical data and information from about 500 patients.

In terms of what’s ahead, many therapies today aren’t targeted to the individual, so Johnny’s brain-oxygen demand may not be the same as Sarah’s brain-oxygen demand, even if they both have congenital heart disease. As a patient waits for surgery, we also have found that the brain-oxygen demand increases, but if the demand is not met, this can lead to pre-operative brain injury. This technology could change the whole conversation about the timing of surgery. In addition, we can measure the brain-oxygen demand intraoperatively. We are finding that we can actually define the right perfusion strategy for each patient, rather than making uniform decisions for all patients with a shared diagnosis.

Lastly, beyond the operating room, we can use this technology for countless conditions. It would help with the treatment of almost any disease in the critical care unit, when we are using tools like ECMO (extracorporeal membrane oxygenation, a salvage technique), and we need to monitor a patient’s status. We can also use it to measure intracranial pressure. In very simple terms, if a child with a shunt comes into the emergency room with a headache, we can noninvasively measure the pressure and see how it’s changed without a head CT. We can decide who needs to go to the operating room – and who doesn’t – without radiation.

Q: How did your career bring you to this point?

A: My interest has always been in brain injury and kids with congenital heart disease. Years ago, I started out using MRI because it was the technology that was bright and shiny at the time. I was part of a team that developed an MRI sequence for measuring cerebral blood flow. We made some discoveries that indicated the culprit for brain injury was not the surgeries. Instead, there was something with the babies.

Unfortunately, with MRI, it’s a big, expensive instrument, and you have to take the baby to the machine for a single point-in-time measurement. So I started working with a physicist at the University of Pennsylvania to develop a way to measure the motion of particles, specifically red blood cells, to study cerebral blood flow. We found ways to use light, and this is what I hope to build and commercialize at Children’s National. By the end of my career, I hope to be able to say that we got this into clinical care.

Cayden rides a horse with her father

Earliest hybrid HLHS heart surgery kids thrive 5 years later

Cayden rides a horse with her father

Five years ago, Cayden was born 6 weeks early weighing less than four pounds and at risk of dying from her critical congenital heart disease. Today, she’s a happy five-year-old who is excited to start kindergarten this fall.

Five years ago, Cayden was born 6 weeks early weighing less than four pounds and at risk of dying from her critical congenital heart disease. Today, she’s a happy five-year-old who is excited to start kindergarten this fall.

Early diagnosis of her hypoplastic right ventricle, double inlet left ventricle and critical coarctation of the aorta allowed for the team at Children’s National Hospital to create a careful plan for safe delivery and to offer an innovative hybrid HLHS surgical approach at the hospital within 24 hours after she was born.

“Truly in my own heart, I do not believe Cayden would be alive today without Dr. Yerebakan and those early hybrid procedures,” says her mom, Casey.

Can Yerebakan, M.D., associate chief of Cardiac Surgery, and Joshua Kanter, M.D., director of Interventional Cardiology, have performed more of these hybrid procedures together at Children’s National than just about anywhere else in the United States. And they are the only team in the country using a special toothpick-sized flexible stent in the ductus. They worked directly with the U.S. Food and Drug Administration to bring these right-sized tiny stents to the U.S. from Europe.

Cayden was one of the first babies to benefit from this cutting-edge approach. In the five-plus years since then, more than 50 high-risk babies, some born as early as 28 weeks of gestation or weighing as little as 2 pounds at birth, have also benefited from hybrid procedures. Soon, the team will start performing hybrid procedures with catheters only, preventing an incision in the chest. This will allow the smallest babies to get the care they need with fewer open-chest procedures.

Read the rest of Cayden’s story here.

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Children’s National in the News: 2023

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Explore some of the notable medical advancements and stories of bravery that defined 2023, showcasing the steadfast commitment of healthcare professionals at Children’s National Hospital and the resilient spirit of the children they support. Delve into our 2023 news highlights for more.

1. COVID during pregnancy dramatically increases the risk of complications and maternal death, large new study finds

According to a study published in British Medical Journal Global Health, women who get COVID during pregnancy are nearly eight times more likely to die and face a significantly elevated risk of ICU admission and pneumonia. Sarah Mulkey, M.D., prenatal-neonatologist neurologist, discussed findings based on her work with pregnant women and their babies.
(Fortune)

2. Rest isn’t necessarily best for concussion recovery in children, study says

A study led by Christopher Vaughan, Psy.D., pediatric neuropsychologist, suggests that — despite what many people may presume — getting kids back to school quickly is the best way to boost their chance for a rapid recovery after a concussion.
(CNN)

3. Pediatric hospital beds are in high demand for ailing children. Here’s why

David Wessel, M.D., executive vice president, chief medical officer and physician-in-chief, explained that one reason parents were still having trouble getting their children beds in a pediatric hospital or a pediatric unit after the fall 2022 respiratory surge is that pediatric hospitals are paid less by insurance.
(CNN)

4. Anisha Abraham details impact of social media use on children: ‘True mental health crisis’

Anisha Abraham, M.D., M.P.H., chief of the Division of Adolescent and Young Adult Medicine, joined America’s Newsroom to discuss the impact social media access has had on children’s mental health.
(FOX News)

5. Saving Antonio: Can a renowned hospital keep a boy from being shot again?

After 13-year-old Antonio was nearly killed outside his mom’s apartment, Children’s National Hospital went beyond treating his bullet wounds. Read how our Youth Violence Intervention Program team supported him and his family during his recovery.
(The Washington Post)

6. Formerly conjoined twins reunite with doctors who separated them

Erin and Jade Buckles underwent a successful separation at Children’s National Hospital. Nearly 20 years later they returned to meet with some of the medical staff who helped make it happen.
(Good Morning America)

7. Asthma mortality rates differ by location, race/ethnicity, age

Shilpa Patel, M.D., M.P.H., medical director of the Children’s National IMPACT DC Asthma Clinic, weighed in on a letter published in Annals of Allergy, Asthma & Immunology, asserting that the disparities in mortality due to asthma in the United States vary based on whether they occurred in a hospital, ethnicity or race and age of the patient.
(Healio)

8. How one Afghan family made the perilous journey across the U.S.-Mexico border

After one family embarked on a perilous journey from Afghanistan through Mexico to the U.S.-Mexico border, they eventually secured entry to the U.S. where Karen Smith, M.D., medical director of Global Services, aided the family’s transition and provided their daughter with necessary immediate medical treatment.
(NPR)

9. When a child is shot, doctors must heal more than just bullet holes

With the number of young people shot by guns on the rise in the U.S., providers and staff at Children’s National Hospital are trying to break the cycle of violence. But it’s not just the physical wounds though that need treating: young victims may also need help getting back on the right track — whether that means enrolling in school, finding a new group of friends or getting a job.
(BBC News)

10. This 6-year-old is a pioneer in the quest to treat a deadly brain tumor

Callie, a 6-year-old diagnosed with diffuse intrinsic pontine glioma, was treated with low-intensity focused ultrasound (LIFU) at Children’s National Hospital and is the second child in the world to receive this treatment for a brain tumor. LIFU is an emerging technology that experts like Hasan Syed, M.D., and Adrianna Fonseca, M.D., are trialing to treat this fatal childhood brain tumor.
(The Washington Post)

11. F.D.A. approves sickle cell treatments, including one that uses CRISPR

The FDA approved a new genetic therapy, giving people with sickle cell disease new opportunities to eliminate their symptoms. David Jacobsohn, M.B.A., M.D., confirmed that Children’s National Hospital is one of the authorized treatment centers and talked about giving priority to the sickest patients if they are on Vertex’s list.
(The New York Times)

12. 6-year-old fulfils wish to dance in the Nutcracker

After the potential need for open-heart surgery threatened Caroline’s Nutcracker performance, Manan Desai, M.D., a cardiac surgeon, figured out a less invasive procedure to help reduce her recovery time so she could perform in time for the holidays.
(Good Morning America)

AI system that can detect RHD

Novel AI platform matches cardiologists in detecting rheumatic heart disease

Artificial intelligence (AI) has the potential to detect rheumatic heart disease (RHD) with the same accuracy as a cardiologist, according to new research demonstrating how sophisticated deep learning technology can be applied to this disease of inequity. The work could prevent hundreds of thousands of unnecessary deaths around the world annually.

Developed at Children’s National Hospital and detailed in the latest edition of the Journal of the American Heart Association, the new AI system combines the power of novel ultrasound probes with portable electronic devices installed with algorithms capable of diagnosing RHD on echocardiogram. Distributing these devices could allow healthcare workers, without specialized medical degrees, to carry technology that could detect RHD in regions where it remains endemic.

RHD is caused by the body’s reaction to repeated Strep A bacterial infections and can cause permanent heart damage. If detected early, the condition is treatable with penicillin, a widely available antibiotic. In the United States and other high-income nations, RHD has been almost entirely eradicated. However, in low- and middle-income countries, it impacts the lives of 40 million people, causing nearly 400,000 deaths a year.

“This technology has the potential to extend the reach of a cardiologist to anywhere in the world,” said Kelsey Brown, M.D., a cardiology fellow at Children’s National and co-lead author on the manuscript with Staff Scientist Pooneh Roshanitabrizi, Ph.D. “In one minute, anyone trained to use our system can screen a child to find out if their heart is demonstrating signs of RHD. This will lead them to more specialized care and a simple antibiotic to prevent this degenerative disease from critically damaging their hearts.”

The big picture

AI system that can detect RHD

The new AI system combines the power of novel ultrasound probes with portable electronic devices installed with algorithms capable of diagnosing RHD on echocardiogram.

Millions of citizens in impoverished countries have limited access to specialized care. Yet the gold standard for diagnosing RHD requires a highly trained cardiologist to read an echocardiogram — a non-invasive and widely distributed ultrasound imaging technology. Without access to a cardiologist, the condition may remain undetected and lead to complications, including advanced cardiac disease and even death.

According to the new research, the AI algorithm developed at Children’s National identified mitral regurgitation in up to 90% of children with RHD. This tell-tale sign of the disease causes the mitral valve flaps to close improperly, leading to backward blood flow in the heart.

Beginning in March, Craig Sable, M.D., interim division chief of Cardiology, and his partners on the project will implement a pilot program in Uganda incorporating AI into the echo screening process of children being checked for RHD. The team believes that a handheld ultrasound probe, a tablet and a laptop — installed with the sophisticated, new algorithm — could make all the difference in diagnosing these children early enough to change outcomes.

“One of the most effective ways to prevent rheumatic heart disease is to find the patients that are affected in the very early stages, give them monthly penicillin for pennies a day and prevent them from becoming one of the 400,000 people a year who die from this disease,” Dr. Sable said. “Once this technology is built and distributed at a scale to address the need, we are optimistic that it holds great promise to bring highly accurate care to economically disadvantaged countries and help eradicate RHD around the world.”

Children’s National Hospital leads the way

To devise the best approach, two Children’s National experts in AI — Dr. Roshanitabrizi and Marius George Linguraru, D.Phil., M.A., M.Sc., the Connor Family Professor in Research and Innovation and principal investigator in the Sheikh Zayed Institute for Pediatric Surgical Innovation — tested a variety of modalities in machine learning, which mimics human intelligence, and deep learning, which goes beyond the human capacity to learn. They combined the power of both approaches to optimize the novel algorithm, which is trained to interpret ultrasound images of the heart to detect RHD.

Already, the AI algorithm has analyzed 39 features of hearts with RHD that cardiologists cannot detect or measure with the naked eye. For example, cardiologists know that the heart’s size matters when diagnosing RHD. Current guidelines lay out diagnostic criteria using two weight categories — above or below 66 pounds — as a surrogate measure for the heart’s size. Yet the size of a child’s heart can vary widely in those two groupings.

“Our algorithm can see and make adjustments for the heart’s size as a continuously fluid variable,” Dr. Roshanitabrizi said. “In the hands of healthcare workers, we expect the technology to amplify human capabilities to make calculations far more quickly and precisely than the human eye and brain, saving countless lives.”

Among other challenges, the team had to design new ways to teach the AI to handle the inherent clinical differences found in ultrasound images, along with the complexities of evaluating color Doppler echocardiograms, which historically have required specialized human skill to evaluate.

“There is a true art to interpreting this kind of information, but we now know how to teach a machine to learn faster and possibly better than the human eye and brain,” Dr. Linguraru said. “Although we have been using this diagnostic and treatment approach since World War II, we haven’t been able to share this competency globally with low- and middle-income countries, where there are far fewer cardiologists. With the power of AI, we expect that we can, which will improve equity in medicine around the world.”

2023 with a lightbulb

The best of 2023 from Innovation District

2023 with a lightbulbAdvanced MRI visualization techniques to follow blood flow in the hearts of cardiac patients. Gene therapy for pediatric patients with Duchenne muscular dystrophy. 3D-printed casts for treating clubfoot. These were among the most popular articles we published on Innovation District in 2023. Read on for our full list.

1. Advanced MRI hopes to improve outcomes for Fontan cardiac patients

Cardiac imaging specialists and cardiac surgeons at Children’s National Hospital are applying advanced magnetic resonance imaging visualization techniques to understand the intricacies of blood flow within the heart chambers of children with single ventricle heart defects like hypoplastic left heart syndrome. The data allows surgeons to make critical corrections to the atrioventricular valve before a child undergoes the single ventricle procedure known as the Fontan.
(3 min. read)

2. Children’s National gives first commercial dose of new FDA-approved gene therapy for Duchenne muscular dystrophy

Children’s National Hospital became the first pediatric hospital to administer a commercial dose of Elevidys (delandistrogene moxeparvovec-rokl), the first gene therapy for the treatment of pediatric patients with Duchenne muscular dystrophy (DMD). Elevidys is a one-time intravenous gene therapy that aims to delay or halt the progression of DMD by delivering a modified, functional version of dystrophin to muscle cells.
(2 min. read)

3. New model to treat Becker Muscular Dystrophy

Researchers at Children’s National Hospital developed a pre-clinical model to test drugs and therapies for Becker Muscular Dystrophy (BMD), a debilitating neuromuscular disease that is growing in numbers and lacks treatment options. The work provides scientists with a much-needed method to identify, develop and de-risk drugs for patients with BMD.
(2 min. read)

4. First infants in the U.S. with specially modified pacemakers show excellent early outcomes

In 2022, five newborns with life-threatening congenital heart disease affecting their heart rhythms were the first in the United States to receive a novel modified pacemaker generator to stabilize their heart rhythms within days of birth. Two of the five cases were cared for at Children’s National Hospital. In a follow-up article, the team at Children’s National shared that “early post-operative performance of this device has been excellent.”
(2 min. read)

5. AI: The “single greatest tool” for improving access to pediatric healthcare

Experts from the Food and Drug Administration, Pfizer, Oracle Health, NVIDIA, AWS Health and elsewhere came together to discuss how pediatric specialties can use AI to provide medical care to kids more efficiently, more quickly and more effectively at the inaugural symposium on AI in Pediatric Health and Rare Diseases, hosted by Children’s National Hospital and the Fralin Biomedical Research Institute at Virginia Tech.
(3 min. read)

6. AAP names Children’s National gun violence study one of the most influential articles ever published

The American Academy of Pediatrics (AAP) named a 2019 study led by clinician-researchers at Children’s National Hospital one of the 12 most influential Pediatric Emergency Medicine articles ever published in the journal Pediatrics. The findings showed that states with stricter gun laws and laws requiring universal background checks for gun purchases had lower firearm-related pediatric mortality rates but that more investigation was needed to better understand the impact of firearm legislation on pediatric mortality.
(2 min. read)

7. Why a colorectal transition program matters

Children’s National Hospital recently welcomed pediatric and adult colorectal surgeon Erin Teeple, M.D., to the Division of Colorectal and Pelvic Reconstruction. Dr. Teeple is the only person in the United States who is board-certified as both a pediatric surgeon and adult colorectal surgeon, uniquely positioning her to care for people with both acquired and congenital colorectal disease and help them transition from pediatric care to adult caregivers.
(3 min. read)

8. First-of-its-kind holistic program for managing pain in sickle cell disease

The sickle cell team at Children’s National Hospital received a grant from the Founders Auxiliary Board to launch a first-of-its-kind, personalized holistic transformative program for the management of pain in sickle cell disease. The clinic uses an inter-disciplinary approach of hematology, psychology, psychiatry, anesthesiology/pain medicine, acupuncture, mindfulness, relaxation and aromatherapy services.
(3 min read)

9. Recommendations for management of positive monosomy X on cell-free DNA screening

Non-invasive prenatal testing using cell-free DNA (cfDNA) is currently offered to all pregnant women regardless of the fetal risk. In a study published in the American Journal of Obstetrics and Gynecology, researchers from Children’s National Hospital provided context and expert recommendations for maternal and fetal evaluation and management when cfDNA screening is positive for monosomy X or Turner Syndrome.
(2 min. read)

10. Innovation in clubfoot management using 3D anatomical mapping

While clubfoot is relatively common and the treatment is highly successful, the weekly visits required for Ponseti casting can be a significant burden on families. Researchers at Children’s National Hospital are looking for a way to relieve that burden with a new study that could eliminate the weekly visits with a series of 3D-printed casts that families can switch out at home.
(1 min. read)

11. Gender Self-Report seeks to capture the gender spectrum for broad research applications

A new validated self-report tool provides researchers with a way to characterize the gender of research participants beyond their binary designated sex at birth. The multi-dimensional Gender Self-Report, developed using a community-driven approach and then scientifically validated, was outlined in a peer-reviewed article in the American Psychologist, a journal of the American Psychological Association.
(2 min. read)

12. Cardiovascular and bone diseases in chronic kidney disease

In a study published by Advances in Chronic Kidney Disease, a team at Children’s National Hospital reviewed cardiovascular and bone diseases in chronic kidney disease and end-stage kidney disease patients with a focus on pediatric issues and concerns.
(1 min. read)

Yves d’Udekem, M.D., Ph.D.,

Evidence and expertise drive cardiac surgery innovation at Children’s National Hospital

Yves d’Udekem, M.D., Ph.D.,

“Our goal is to do the difficult and the impossible,” says Yves d’Udekem, M.D., Ph.D.

“Our goal is to do the difficult and the impossible,” says Yves d’Udekem, M.D., Ph.D., chief of Cardiac Surgery at Children’s National Hospital.

Dr. d’Udekem and the cardiac surgeons at Children’s National apply technical skill and expertise to offer renewed hope for the highest risk children with critical congenital heart disease, including those with single ventricle anomalies like hypoplastic left heart syndrome.

“When families have nowhere else to turn, they can turn to us,” he adds.

Why it matters

The cardiac surgery team has welcomed families from across the United States and around the world who seek experts in the care of these critical heart conditions. Their experience is building an important evidence base for better surgical approaches that will improve long-term outcomes for children with many different types of congenital heart disease, but especially for single ventricle conditions.

Innovation in cardiac surgery

  • Hybrid surgical strategy: Cardiac Surgeon Can Yerebakan, M.D., and Interventional Cardiology Director Joshua Kanter, M.D., are national leaders in the use of a hybrid surgical strategy for high-risk infants with single ventricle heart conditions. They can perform this procedure on babies as small as 1.1 kilograms. It allows critical time for the lungs and other organs to recover and get stronger after birth before the child undergoes more invasive procedures.
  • New uses for artificial hearts: d’Udekem showed proof-of-concept for the use of an artificial heart to give a child with a single ventricle the time for their own heart to recover rather than being transplanted. In this case, the child was supported by a left-ventricle assist device (LVAD) long term. As their own heart recovered, surgeons then performed successful procedures that seemed impossible to perform before.
  • Novel complex pulmonary artery reconstruction: Children’s National performs the most complex lobar and sub-lobar pulmonary artery reconstruction for children with complex pulmonary stenosis. Cardiac Surgeon Manan Desai, M.D., says the approach leverages interventional cardiac imaging and precision surgical techniques to correct stenosis in smaller lung arteries. This helps establish better right-sided pressure in the heart and likely reduces the chance of heart failure down the road.
  • Pediatric-focused advanced lung care and transplant: Children’s National is poised to become one of only a few locations in the United States to offer comprehensive care for children with complex lung conditions. In 2024, Cardiac Surgeon Aybala Tongut, M.D., will begin performing pediatric lung transplants as part of the hospital’s Advanced Lung Disease Program focused on the unique needs of children.

Children’s National leads the way

“It’s time to combine firsthand expertise and long-term outcomes from decades of congenital heart surgical procedures to refine our surgical techniques,” says Dr. d’Udekem. “We need to ensure patients with congenital heart disease, especially those with single ventricle heart defects, can thrive long term.”
animation showing MRI cardiac imaging

Soon, the Children’s National team plans to re-examine the effectiveness of different techniques for the Fontan procedure. They’ll compare an extracardiac approach against the older lateral tunnel procedure to determine how best to reduce long-term pressure on the heart by creating larger conduits and improving blood flow.

More education is needed to ensure valve repairs for children with congenital heart disease, including single ventricle conditions, which have a high rate of failure and require reoperation, are as successful as can be. The goal is to avoid the need for reoperation or replacement procedures. This is why Children’s National recently hosted the inaugural Valve Repair Symposium. It featured practical cases illustrated with intraoperative video, echocardiography and MR images to bring critical knowledge about pediatric heart valve repair to more people in the field.

Drs. Catherine Limperopoulos, Yao Wu and David Wessel

AHA’s Outstanding Research Award: Three generations of pediatric cardiac excellence

Drs. Catherine Limperopoulos, Yao Wu and David Wessel

Catherine Limperopoulos, Ph.D., Yao Wu, Ph.D., and David Wessel, M.D.

Children’s National Hospital is celebrating a remarkable milestone as three of its faculty members have been honored over 15 years with the American Heart Association’s Outstanding Research in Pediatric Cardiology Award. Yao Wu, Ph.D., became the latest researcher to earn the accolade for her groundbreaking work into congenital heart disease (CHD).

A research faculty member with the newly established Center for Prenatal, Neonatal & Maternal Health Research, Dr. Wu received the award specifically for her studies on the role of altered placental function, measured by advanced in utero imaging, and neurodevelopmental outcomes in toddlers with CHD.

Honored at the association’s annual meeting in Philadelphia, Dr. Wu returned to Children’s National to warm congratulations from her colleagues who had previously won the award: David Wessel, M.D., executive vice president and chief medical officer, and Catherine Limperopoulos, Ph.D., director of the new center.

“I am thrilled to pass the baton to one of our own,” Dr. Limperopoulos said. “Dr. Wu’s recognition speaks to the outstanding and innovative research happening at Children’s National among junior faculty who are focusing on advancing our understanding of congenital heart disease and its long-term neurodevelopmental outcomes.”

Why we’re excited

The prestigious award represents more than individual accomplishments; it symbolizes three generations of mentorship and collaboration at the hospital. In 2007, Dr. Wessel joined Children’s National to enhance the care of newborns across specialty services by expanding programs and research, with a focus on critically ill newborns with heart disease. He recruited and mentored Dr. Limperopoulos in 2010, who became one of his research partners and creator of the hospital’s Center for Prenatal, Neonatal & Maternal Health Research. Dr. Limperopoulos, in turn, recruited and mentored Dr. Wu, providing her with the tools to conduct advanced imaging on in-utero brains and placentas, as well as the development of children with CHD.

“Each one of us is in different phases of our careers, yet we are connected by our deep interest in advancing cardiac care for critically ill newborns,” Dr. Wessel said. “In this collaborative environment, we learn from each other to improve entire lifetimes for our patients.”

Dr. Wu said she believes in sharing scientific developments for the advancement of the entire medical community. “It was an honor to be chosen to join this esteemed club, which has a relentless focus on improving health outcomes,” she said.

Children’s National leads the way

The award winners shared five collaborations published in leading journals to contribute to the ongoing dialogue in the field and the innovative work happening at Children’s National:

screenshot from Congenital Heart Initiative (CHI) Registry Participant Timeline

Congenital Heart Initiative beat recruitment goals, kicked off patient-engaged studies in year three

The Congenital Heart Initiative (CHI) is celebrating its third year as the first global patient-powered registry for adults with congenital heart disease (CHD). In 2023, the registry surpassed recruitment targets and launched a data intake process to allow researchers from around the world to submit proposals for patient-centered research and programs around the critical questions for adults with CHD who had their hearts repaired in childhood.

What it means

By recruiting over 4,600 participants in all 50 states and 37 countries, the CHI is now the largest patient-powered registry for adults with congenital heart disease. This is the first time researchers and clinicians have been able to access this type of robust data set to help them better understand and address the needs of people with CHD as they continue to age. Even better, the registry’s mechanisms allow for routine feedback and input about priorities directly from the growing patient population.

“Patient-centered research organizations, not providers or universities, have the greatest ability to lead this charge and lay the foundation for future breakthroughs. The inspiring efforts of all participants to date gives me hope that the next generation of advances is within reach,” says Matthew Lewis, M.D., an adult congenital heart specialist and CHI-RON site PI from Columbia University Medical Center.

An ongoing sub-study of CHI uses PCORnet®, the National Patient-Centered Clinical Research Network, to better understand how gaps in care impact the adult patient experience with CHD. The CHI-RON study (PCORI RD-2020C2-20347) fills in these gaps by exploring three distinct data types: patient-reported outcomes, health insurance claims and electronic health records. The effort is led by Children’s National Hospital and Louisiana Public Health Institute.

This year, CHI also launched some of its first studies, focused on pregnancy, health disparities and long-term health care follow-ups. The first academic manuscripts about these studies are expected to publish in the next year.

Why it matters

Although nearly 2 million adults in the United States are living with a congenital heart defect — more adults than children in fact — it’s been historically difficult to gather data on these conditions and to identify patient needs.

As children born with CHD become adults, they have a lot of worry and uncertainty about their limitations and abilities to achieve what might be considered common adult milestones. The research made possible by this registry and the mechanisms to communicate findings to both the participants and the larger clinical community will make a big difference in quality of life and hope to provide more answers to these important questions.

The CHI related meetings have allowed a space where patients and researchers can come together to discuss research priorities.

“Once you go and look at things from the patient’s point of view, there is no going back. It is going to be something that will redefine you as a researcher and a provider,” says Rohan D’Souza, M.D., a maternal-fetal medicine specialist who is an active participant in a PCORI-funded maternal health consortium focused on reducing maternal morbidity and mortality in CHD patients (PCORI EACB-23293).

The patient benefit

Additionally, because people with CHD live all over the United States and the world, it can be hard for them to connect with each other to share common questions and experiences with clinicians and each other. The patient-driven registry engages participants and hopes to help make greater connections between people who live with CHD. A key registry partner, the Adult Congenital Heart Association (ACHA), helps create opportunities, such as virtual Coffee Hours, for people in the registry to weigh in on research priorities and share feedback about CHI’s work.

“The ACHA Cafe was born out of a need for connection,” says Aliza Marlin, who founded and organized the café project on behalf of the ACHA. “A virtual social hour, coffee optional, gave the ACHD community a safe space to come together. Using it as a conduit to the Congenital Heart Initiative gave us an empowered voice in our own futures. It’s the perfect example of social connection leading to transformative possibilities.”

What’s next

Anitha John, M.D., medical director of the Washington Adult Congenital Heart Program and an adult congenital cardiologist at Children’s National Hospital who leads CHI, says that the future looks bright for the registry and the vital information it can provide.

The new data intake process launched this year, she adds, gives anyone with an interest the ability to submit ideas for new grants, projects and studies. The team will also continue to engage with registry participants, researchers and the centers who provide care for people with CHD, all with the goal of finding more answers to the key questions about how to accomplish specific goals, such as improving mental health, the health care transition and overall quality of life for adults with CHD. For more information on how to get involved, please email ACHDresearch@childrensnational.org.

sonogram showing tetralogy of Fallot

Tetralogy of Fallot repair technique demonstrates low reoperation rates

Cardiac surgeons at Children’s National Hospital have used a uniform transventricular strategy for tetralogy of Fallot repair for more than 15 years. A large, retrospective study published in the Journal of Thoracic and Cardiovascular Surgery demonstrates that few patients who received a repair using this method required a reoperation to implant a pulmonary valve in the first 10 years after their primary repair surgery.

What it is

The study is one of the first to report statistically significant outcomes of the transventricular approach applied uniformly in a single institution. It provides tangible evidence of the short- and mid-term postoperative outcomes from 244 consecutive patients who underwent tetralogy of Fallot repair at Children’s National between 2004 and 2019. Infants received the repair between 42 and 106 days after birth.

Tetralogy of Fallot is a condition of several related congenital heart defects that occur due to abnormal development of the prenatal heart during the first eight weeks of pregnancy.

Why it matters

The data show that, at Children’s National, 96.7% of children who underwent tetralogy of Fallot repair within the first year of life using this transventricular approach were able to avoid having an additional surgery to receive a replacement pulmonary valve for up to a decade after their initial repair.

It also shows a benefit of this approach soon after birth. The authors believe that having the repair earlier (on average, 71 days after birth in this study) provides long-term benefits to the growth and development of both the brain and heart. The repair also protects the heart’s function over time by preventing the development of dangerous ventricular arrhythmias.

The big picture

Short- and mid-term post-surgical outcome data like the information presented in this study are an important indicator of the expertise, care quality and overall safety associated with the cardiac surgery team performing the procedure.

These findings provide critical insight into the effectiveness of specific treatment approaches for infants with tetralogy of Fallot and can help both clinicians and families better understand the benefits and risks of these procedures.

Read the full study in the Journal of Thoracic and Cardiovascular Surgery.

ARPA-H logo

Children’s National selected as member of ARPA-H Investor Catalyst Hub spoke network

ARPA-H logoThe hospital will advocate for the unique needs of children as part of nationwide network working to accelerate transformative health solutions.

Children’s National Hospital was selected as a spoke for the Investor Catalyst Hub, a regional hub of ARPANET-H, a nationwide health innovation network launched by the Advanced Research Projects Agency for Health (ARPA-H).

The Investor Catalyst Hub seeks to accelerate the commercialization of groundbreaking and accessible biomedical solutions. It uses an innovative hub-and-spoke model designed to reach a wide range of nonprofit organizations and Minority-Serving Institutions, with the aim of delivering scalable healthcare outcomes for all Americans.

“The needs of children often differ significantly from those of adults. This partnership reflects our commitment to advancing pediatric healthcare through innovation and making sure we’re addressing those needs effectively,” said Kolaleh Eskandanian, Ph.D., M.B.A., vice president and chief innovation officer at Children’s National. “Leveraging the strength of this hub-and-spoke model, we anticipate delivering transformative solutions to enhance the health and well-being of the patients and families we serve.”

Children’s National joins a dynamic nationwide network of organizations aligned to ARPA-H’s overarching mission to improve health outcomes through the following research focus areas: health science futures, proactive health, scalable solutions and resilient systems. Investor Catalyst Hub spokes represent a broad spectrum of expertise, geographic diversity and community perspectives.

“Our spoke network embodies a rich and representative range of perspectives and expertise,” said Mark Marino, vice president of Growth Strategy and Development for VentureWell and project director for the Investor Catalyst Hub. “Our spokes comprise a richly diverse network that will be instrumental in ensuring that equitable health solutions reach communities across every state and tribal nation.”

As an Investor Catalyst Hub spoke, Children’s National gains access to potential funding and flexible contracting for faster award execution compared to traditional government contracts. Spoke membership also offers opportunities to provide input on ARPA-H challenge areas and priorities, along with access to valuable networking opportunities and a robust resource library.

Alliance for Pediatric Device Innovation consortium members

Children’s National awarded nearly $7.5 million by FDA to lead pediatric device innovation consortium

Alliance for Pediatric Device Innovation consortium membersChildren’s National Hospital was awarded nearly $7.5 million in a five-year grant to continue its leadership of an FDA-funded pediatric device consortium. Building upon a decade of previous consortium leadership, the new consortium is Alliance for Pediatric Device Innovation (APDI) and features a new and expanded roster of partners that reflects its added focus on providing pediatric innovators with expert support on evidence generation, including the use of real-world evidence (RWE), for pediatric device development.

Collaborating for success

With the goal of helping more pediatric medical devices complete the journey to commercialization, APDI is led by Children’s National, with Kolaleh Eskandanian, Ph.D., M.B.A., vice president and chief innovation officer, serving as program director and principal investigator, and Julia Finkel, M.D., pediatric anesthesiologist and director of Pain Medicine Research and Development in the Sheikh Zayed Institute for Pediatric Surgical Innovation, serving as principal investigator.

Consortium members include Johns Hopkins University, CIMIT at Mass General Brigham, Tufts Medical Center, Medstar Health Research Institute and MedTech Color. Publicly traded OrthoPediatrics Corp., which exclusively focuses on advancing pediatric orthopedics, is serving as APDI’s strategic advisor and role model for device innovators whose primary focus is children.

Why we’re excited

Consortium initiatives got underway quickly with the announcement of a special MedTech Color edition of the “Make Your Medical Device Pitch for Kids!”competition that focuses on African American and Hispanic innovators. Interested innovators can find details and apply at MedTech Color Pitch Competition. The competition was announced at the recent MedTech Color networking breakfast on Oct. 10,2023 at The MedTech Conference powered by AdvaMed.

“We all benefit from greater equity and inclusion among pediatric MedTech founders, decision-makers, investigators and developers in more effectively addressing the needs of the entire pediatric population,” said Eskandanian. “We need the expertise and insights of innovators from diverse backgrounds, and we want to provide these talented individuals with more opportunities to present their work and share their perspectives on pediatric device development.”

Additional details

APDI is one of five FDA-funded consortia created to provide a platform of services, expertise and funding to help pediatric innovators bring medical devices to the market that specifically address the needs of children.

 

boy in hospital bed

Local context, health system integrations key to sustainable interventions after RHD diagnosis

boy in hospital bed

Although entirely preventable, RHD, a disease of poverty and social disadvantage resulting in high morbidity and mortality, remains an ever-present burden in low- and middle-income countries, as well as rural, remote, marginalized and disenfranchised populations within high-income countries.

A rheumatic heart disease (RHD) work group convened by the National Heart, Lung, and Blood Institute (NHLBI) concludes that any priority intervention strategies to slow or stop late complications of RHD need to consider local contexts and should be integrated into health systems to meet the affected community’s needs in a sustainable way.

The group outlined priorities based on current available evidence to support the development and implementation of accessible, affordable and sustainable interventions in low-resource settings to manage RHD and its related complications.

Craig Sable, M.D., associate chief of Cardiology at Children’s National Hospital, served as a senior author on the recommendations, based on the work group findings.

Why it matters

Although entirely preventable, RHD, a disease of poverty and social disadvantage resulting in high morbidity and mortality, remains an ever-present burden in low- and middle-income countries, as well as rural, remote, marginalized and disenfranchised populations within high-income countries.

The NHLBI workshop sought to support RHD eradication efforts worldwide by:

  • Analyzing the current state of science
  • Identifying basic science and clinical research priorities

Each work group was assigned to review existing guidelines and research for different stages of the disease’s progression, which is now being published together as a set of five companion articles to raise the prioritization of RHD research and funding.

Moving the field forward

Due to the high prevalence of RHD in low- and middle-income countries, Dr. Sable’s work group focused on gaining a better understanding of the needs in the field from the five perspectives: people living with RHD, the community, healthcare providers, health systems and policymakers.

They identified several priorities and strategies, and they stressed that any interventional strategy, now or in the future, must be culturally safe and community-driven to ensure the creation of a locally and culturally relevant, sustainable continuum of care for people from historically marginalized populations.

What’s next

The authors emphasize that that over 300,000 deaths per year are the result of inadequate, underfunded and poorly integrated care. “Global vision and leadership to enact and implement available policies are needed to close large research gaps in all aspects at patient, health system and policy levels. Robust research and development are urgently needed to improve comprehensive tertiary care and ensure implementation of evidence-based interventions, while developing new innovations, technologies and interventions.”

You can read all the working group manuscripts, including this one: Tertiary Prevention and Treatment of Rheumatic Heart Disease: A National Heart, Lung, and Blood Institute Working Group Summary, in BMJ Global Health.

Learn more about the challenges of rheumatic heart disease in sub-Saharan Africa and other developing parts of the world through the Rheumatic Heart Disease microdocumentary series:

pregnant woman looking at sonogram

Babies with congenital heart disease display disrupted brain function before birth

pregnant woman looking at sonogram

In their study, the team at Children’s National Hospital found that specific brain regions become especially vulnerable to injury around 24 weeks of pregnancy when developing babies begin to have high energy demands and rapid neurovascular changes.

For the first time, researchers have found that babies born with congenital heart disease (CHD) have alterations to the emerging functional connectivity of their brains in utero. The changes are related to the subtype of their CHD and their oxygen status before they have lifesaving surgery to treat their cardiac malformation, according to new findings published in the American Heart Association’s Circulation Research.

In their study, the team at Children’s National Hospital found that specific brain regions become especially vulnerable to injury around 24 weeks of pregnancy when developing babies begin to have high energy demands and rapid neurovascular changes. That leaves certain parts of the brain, including the brainstem, more susceptible to injury from cardiac complications and poor circulation.

“We used a special type of magnetic resonance imaging to safely study the brains of these unborn babies, and we found that they have weakened connectivity in the deep grey structures, which are responsible for sensation, movement, alertness and other core functions,” said Josepheen De Asis-Cruz, M.D., Ph.D., assistant professor at the Developing Brain Institute at Children’s National and an author of the study. “This offers an important clue in utero to the type of care the babies will eventually need when they are born.”

The big picture

In the past decade, the survival rate for fetuses with CHD has greatly improved. About 80% of cases – even some of the most high-risk heart defects – can be successfully treated or palliated with surgery and survive. Yet Dr. Cruz said researchers are finding that the rates of poor neurodevelopmental outcomes are about the same. That’s why she and her colleagues are looking at what precisely may be injuring the brains of these newborns prior to surgery, offering a possible roadmap to interventions.

The fine print

The research team studied 107 healthy, low-risk pregnancies and 75 pregnancies known to be complicated by CHD. They used functional connectivity magnetic resonance imaging (fcMRI) to examine the emerging connections of the brains of unborn babies, given fcMRI’s unique ability to query the brain in a resting state when a patient is unable to respond to tasks. They also studied the oxygen saturation levels of the babies after they were born and then mapped all of this information to the type of CHD that they were diagnosed with.

“Our findings indicate that the compromised connectivity in the brains of CHD patients before delivery is linked to hypoxia after birth,” Cruz said. “There were important differences in the low- and high-risk CHD groups. Babies born with transposition of the great arteries or hypoplastic left heart syndrome – two of the most high-risk diagnoses – have notable changes in their brain function, which could someday be used as biomarkers to guide their care.”

What’s ahead

Researchers at Children’s National are working together, using a variety of modalities, to move toward precision imaging in utero to help predict a child’s neurodevelopmental outcomes. The ultimate goal: better interventions sooner.

“This work is foundational. As we fine-tune more techniques to identify babies at risk, we can understand how environmental, genetic and epigenetic factors impact brain development and guide care decisions,” said Catherine Limperopoulos, Ph.D., director of the Center for Prenatal, Neonatal & Maternal Health Research and a senior author of the paper. “We can imagine a day where we can offer pregnant mothers highly detailed and personalized information about their unborn baby, and individualized interventions that lead to healthier lifetimes.”

doctor listening to child's heartbeat

Earlier detection of cardiometabolic risk factors for kids may be possible through next generation biomarkers

doctor listening to child's heartbeat

The next generation of cardiometabolic biomarkers should pave the way for earlier detection of risk factors for conditions such as obesity, diabetes and heart disease in children.

American Heart Association statement finds potential future measures, reiterates importance of heart-healthy lifestyle from birth through adulthood.

The next generation of cardiometabolic biomarkers should pave the way for earlier detection of risk factors for conditions such as obesity, diabetes and heart disease in children, according to a new scientific statement from the American Heart Association published in the journal Circulation.

“The rising number of children with major risk factors for cardiometabolic conditions represents a potential tsunami of preventable disease for our healthcare system,” says the statement’s lead author Michele Mietus-Snyder, M.D., a preventive cardiologist and clinical research scientist at Children’s National Hospital. “But by the time a child is identified based on today’s clinical biomarkers, it’s often too late to reverse the disease trajectory.”

The big picture

The scientific statement included biomarkers that met three criteria:

  • Early and precise clinical detection of metabolic abnormalities before a child begins to show the current clinical signs such as high body mass index (BMI), blood pressure or cholesterol.
  • Mechanistic intervention targets providing immediate risk measures and giving clinicians new targets to personalize and optimize interventions.
  • Modifiable biomarkers that are capable of tracking progression toward or away from cardiometabolic health.

The statement’s identified biomarkers included measures of:

  • Epigenetic, or environmental, factors
  • Gut microbiome health
  • Small particle metabolites in the body
  • Different types of lipids and their impacts on cell membranes
  • Inflammation and inflammatory mediators

The authors proposed these biomarkers with the goal of “expanding awareness to include a whole new realm of biomarkers that precede the traditional risk factors we currently rely upon, such as BMI, blood pressure, cholesterol and blood sugar,” says Mietus-Snyder. “Ideally, these new biomarkers will be added to the array of measures used in clinical research to better assess their value for earlier identification and prevention of global patterns of cardiometabolic health and risk.”

Why it matters

The next generation cardiometabolic biomarkers outlined by the authors are all currently used in research studies and would need to be validated for clinical use. However, Mietus-Snyder notes that the data already collected from these biomarkers in research can make a difference in clinical practice by enhancing our understanding of the deep metabolic roots for children at risk.

Evidence reviewed in the statement shows the risk factors children are exposed to, even before birth, can set the stage for cardiovascular and metabolic health across the lifespan.

Interestingly, all the different factors reviewed have been found to alter the functioning of the mitochondria — the complex organelles responsible for producing the energy for the body that every cell and organ system in turn needs to function. Every class of biomarkers reviewed is also favorably influenced by heart-healthy nutrition, a simple but powerful tool known to improve mitochondrial function.

What’s next

Even as the new so-called ‘omic’ biomarkers reviewed in this statement are developed for clinical applications, there are things clinicians can do to optimize them and improve mitochondrial function, according to Mietus-Snyder.

Most important is to strengthen the collective dedication of care providers to removing the barriers that prevent people, especially expecting mothers and children, from living heart-healthy lifestyles.

We have long known lifestyle factors influence health. Even as complicated metabolic reasons for this are worked out, families can reset their metabolism by decreasing sedentary time and increasing activity, getting better and screen-free sleep, and eating more real foods, especially vegetables, fruits and whole grains, rich in fiber and nutrients, with fewer added sugars, chemicals, preservatives and trans fats. Clinicians can work with their patients to set goals in these areas.

“We know diet and lifestyle are effective to some degree for everyone but terribly underutilized. As clinicians, we have compelling reasons to re-dedicate ourselves to advocating for healthy lifestyle interventions with the families we serve and finding ways to help them implement them as early as possible. The evidence shows the sooner we can intervene for cardiometabolic health, the better.”

Patient and doctor demoing Rare-CAP technology

M.D. in your pocket: New platform allows rare disease patients to carry medical advice everywhere

When someone has a rare disease, a trip to the emergency room can be a daunting experience: Patients and their caregivers must share the particulars of their illness or injury, with the added burden of downloading a non-specialist on the details of a rare diagnosis that may change treatment decisions.

Innovators at Children’s National Hospital and Vanderbilt University Medical Center, supported by Takeda, are trying to simplify that experience using a new web-based platform called the Rare Disease Clinical Activity Protocols, or Rare-CAP. This revolutionary collection of medical information allows patients to carry the latest research-based guidance about their rare disorders in their phones, providing a simple QR code that can open a trove of considerations for any medical provider to evaluate as they work through treatment options for someone with an underlying rare disease.

“No one should worry about what happens when they need medical help, especially patients with rare diseases,” said Debra Regier, M.D., division chief of Genetics and Metabolism at Children’s National and Rare-CAP’s lead medical advisor. “We built this new tool because I have watched as my patient-families have wound up in an emergency room — after all, kids get sprains or fractures — but they don’t have the expertise of a rare disease specialist with them. My hope is that they’re going to pull out their phones and access Rare-CAP, which will explain their rare disease to a new provider who can provide more thoughtful and meaningful care.”

The big picture

A rare disease is defined as any disorder that affects less than 200,000 people in the United States. Some 30 million Americans are believed to be living with one of the 7,000 known rare disorders tracked by the National Organization of Rare Diseases (NORD). Led by Dr. Regier, the Rare Disease Institute at Children’s National is one of 40 NORD centers for excellence in the country that provide care, guidance and leadership for the wide array of disorders that make up the rare disease community.

While a key goal of Rare-CAP is to bolster patient self-advocacy, the platform will also allow medical providers to proactively search for protocols on rare diseases when they know they need specialized advice from experts at Children’s National, a network of tertiary care centers and patient organizations.

As a leading values-based, R&D-driven biopharmaceutical company, Takeda has committed $3.85 million to the project to help activate meaningful change and empower a brighter future for rare disease communities, providing a unique understanding of the struggle that patients and caregivers face when they need care.

“Our team, alongside the medical and rare disease community, saw the need for a single portal to collect standardized care protocols, and we are thrilled to see this innovative tool come to life,” said Tom Koutsavlis, M.D., head of U.S. Medical Affairs at Takeda. “People with rare diseases and their caregivers need faster access to authoritative medical information that providers anywhere can act on, this will lead to improving the standard of care, accelerating time to diagnosis and breaking down barriers to increase equitable access.”

The patient benefit

The creators of Rare-CAP imagined its use in a wide range of settings, including emergency rooms, surgical suites, dental offices, urgent care offices and school clinics. The platform will eventually profile thousands of rare diseases and lay out the implications for care, while also creating a dynamic conversation among users who can offer updates based on real-world experience and changes in medical guidance.

“Our patients are unique, and so is this tool,” Dr. Regier said. “As we roll out Rare-CAP, we believe it is just the beginning of the conversation to expand the platform and see its power for the patient and provider grow, with each entry and each new rare disease that’s added to the conversation.”

Catherine Limperopoulos

Imaging reveals altered brain chemistry of babies with CHD

Researchers at Children’s National Hospital used magnetic resonance spectroscopy to find new biomarkers that reveal how congenital heart disease (CHD) changes an unborn baby’s brain chemistry, providing early clues that could someday guide treatment decisions for babies facing lifelong health challenges.

Published in the Journal of the American College of Cardiology, the findings detail the ways that heart defects disrupt metabolic processes in the developing brain, especially during the third trimester of pregnancy when babies grow exponentially.

“Over the past decade, our team has been at the forefront of developing safe and sophisticated ways to measure and monitor fetal brain health in the womb,” said Catherine Limperopoulos, Ph.D., director of the Center for Prenatal, Neonatal and Maternal Health Research at Children’s National. “By tapping into the power of advanced imaging, we were able to measure certain maturational components of the brain to find early biomarkers for newborns who are going to struggle immediately after birth.”

The fine print

In one of the largest cohorts of CHD patients assembled to date, researchers at Children’s National studied the developing brains of 221 healthy unborn babies and 112 with CHD using magnetic resonance spectroscopy, a noninvasive diagnostic test that can examine chemical changes in the brain. They found:

  • Those with CHD had higher levels of choline and lower levels of N-Acetyl aspartate-to-choline ratios compared to healthy babies, potentially representing disrupted brain development.
  • Babies with more complex CHD also had higher levels of cerebral lactate compared to babies with two ventricle CHD. Lactate, in particular, is a worrying signal of oxygen deprivation.

Specifically, elevated lactate levels were notably increased in babies with two types of heart defects: transposition of the great arteries, a birth defect in which the two main arteries carrying blood from the heart are switched in position, and single ventricle CHD, a birth defect causing one chamber to be smaller, underdeveloped or missing a valve. These critical heart defects generally require babies to undergo heart surgery not long after birth. The elevated lactate levels also were associated with an increased risk of death, highlighting the urgency needed for timely and effective interventions.

The research suggests that this type of imaging can provide a roadmap for further investigation and hope that medicine will someday be able to better plan for the care of these children immediately after their delivery. “With important clues about how a fetus is growing and developing, we can provide better care to help these children not only survive, but thrive, in the newborn period and beyond,” said Nickie Andescavage, M.D., Children’s National neonatologist and first author on the paper.

The big picture

CHD is the most common birth defect in the United States, affecting about 1% of all children born or roughly 40,000 babies each year. While these defects can be fatal, babies who survive are known to be at significantly higher risk of lifelong neurological deficits, including lower cognitive function, poor social interaction, inattention and impulsivity. The impact can also be felt in other organ systems because their hearts did not pump blood efficiently to support development.

Yet researchers are only beginning to pinpoint the biomarkers that can provide information about which babies are going to struggle most and require higher levels of care. The National Institutes of Health (NIH) and the District of Columbia Intellectual and Developmental Disabilities Research Center supported the research at Children’s National to improve this understanding.

“For many years we have known that the brains of children with severe heart problems do not always develop normally, but new research shows that abnormal function occurs already in the fetus,” said Kathleen N. Fenton, M.D., M.S., chief of the Advanced Technologies and Surgery Branch in the Division of Cardiovascular Sciences at the National Heart, Lung, and Blood Institute (NHLBI). “Understanding how the development and function of the brain is already different before a baby with a heart defect is born will help us to intervene with personal treatment as early as possible, perhaps even prenatally, and improve outcomes.”

Note: This research and content are solely the responsibility of the authors and do not necessarily represent the official views of the NIH. The NIH provided support for this research through NHLBI grant R01HL116585 and the Eunice Kennedy Shriver National Institute of Child Health and Human Development grant P50HD105328.

Bone Marrow–Derived MSC Treatment Mitigates Structural Abnormalities Resulting From CPB

Cell therapy mitigates neurological impacts of cardiac surgery in pre-clinical model

Differences of cortical fractional anisotropy between cardiopulmonary bypass and control (left), cardiopulmonary bypass + mesenchymal stromal cells and cardiopulmonary bypass (center), and 3 groups (right).

A pre-clinical study in the journal JACC: Basic to Translational Science shows that infusing bone marrow-derived mesenchymal stromal cells (BM-MSCs) during cardiac surgery provides both cellular-level neuroprotection for the developing brain and improvements in behavior alterations after (or resulting from) surgery.

What this means

According to lead author Nobuyuki Ishibashi, M.D., Oxidative and inflammatory stresses that are thought to be related to cardiopulmonary bypass cause prolonged microglia activation and cortical dysmaturation in the neonatal and infant brain. These issues are a known contributor to neurodevelopmental impairments in children with congenital heart disease.

This study found that, in a pre-clinical model, the innovative use of cardiopulmonary bypass to deliver these mesenchymal stromal cells minimizes microglial activation and neuronal apoptosis (cell death), with subsequent improvement of cortical dysmaturation and behavioral alteration after neonatal cardiac surgery.

Additionally, the authors note that further transcriptomic analyses provided a possible mechanism for the success: Exosome-derived miRNAs such as miR-21-5p, which may be key drivers of the suppressed apoptosis and STAT3-mediated microglial activation observed following BM-MSC infusion.

Why it matters

Significant neurological delay is emerging as one of the most important current challenges for children with congenital heart disease, yet few treatment options are currently available.

Applications of BM-MSC treatment will provide a new therapeutic paradigm for potential MSC-based therapies as a form of neuroprotection in children with congenital heart disease.

Children’s National Hospital leads the way

The Ishibashi lab is the first research team to demonstrate the safety, efficacy and utility of using cardiopulmonary bypass to deliver BM-MSCs with the goal of improving neurological impairments in children undergoing surgery for congenital heart disease. In addition to this pre-clinical research, a phase 1 clinical trial, MeDCaP, is underway at Children’s National.

Recent additional funding from the NIH will allow the team to identify molecular signatures of BM-MSC treatment and mine specific BM-MSC exosomes for unique cardiopulmonary bypass pathology to further increase understanding of precisely how and why this cell-based treatment shows success.