Cardiology & Heart Surgery

Billie Lou Short and Kurt Newman at Research and Education Week

Research and Education Week honors innovative science

Billie Lou Short and Kurt Newman at Research and Education Week

Billie Lou Short, M.D., received the Ninth Annual Mentorship Award in Clinical Science.

People joke that Billie Lou Short, M.D., chief of Children’s Division of Neonatology, invented extracorporeal membrane oxygenation, known as ECMO for short. While Dr. Short did not invent ECMO, under her leadership Children’s National was the first pediatric hospital to use it. And over decades Children’s staff have perfected its use to save the lives of tiny, vulnerable newborns by temporarily taking over for their struggling hearts and lungs. For two consecutive years, Children’s neonatal intensive care unit has been named the nation’s No. 1 for newborns by U.S. News & World Report. “Despite all of these accomplishments, Dr. Short’s best legacy is what she has done as a mentor to countless trainees, nurses and faculty she’s touched during their careers. She touches every type of clinical staff member who has come through our neonatal intensive care unit,” says An Massaro, M.D., director of residency research.

For these achievements, Dr. Short received the Ninth Annual Mentorship Award in Clinical Science.

Anna Penn, M.D., Ph.D., has provided new insights into the central role that the placental hormone allopregnanolone plays in orderly fetal brain development, and her research team has created novel experimental models that mimic some of the brain injuries often seen in very preterm babies – an essential step that informs future neuroprotective strategies. Dr. Penn, a clinical neonatologist and developmental neuroscientist, “has been a primary adviser for 40 mentees throughout their careers and embodies Children’s core values of Compassion, Commitment and Connection,” says Claire-Marie Vacher, Ph.D.

For these achievements, Dr. Penn was selected to receive the Ninth Annual Mentorship Award in Basic and Translational Science.

The mentorship awards for Drs. Short and Penn were among dozens of honors given in conjunction with “Frontiers in Innovation,” the Ninth Annual Research and Education Week (REW) at Children’s National. In addition to seven keynote lectures, more than 350 posters were submitted from researchers – from high-school students to full-time faculty – about basic and translational science, clinical research, community-based research, education, training and quality improvement; five poster presenters were showcased via Facebook Live events hosted by Children’s Hospital Foundation.

Two faculty members won twice: Vicki Freedenberg, Ph.D., APRN, for research about mindfulness-based stress reduction and Adeline (Wei Li) Koay, MBBS, MSc, for research related to HIV. So many women at every stage of their research careers took to the stage to accept honors that Naomi L.C. Luban, M.D., Vice Chair of Academic Affairs, quipped that “this day is power to women.”

Here are the 2019 REW award winners:

2019 Elda Y. Arce Teaching Scholars Award
Barbara Jantausch, M.D.
Lowell Frank, M.D.

Suzanne Feetham, Ph.D., FAA, Nursing Research Support Award
Vicki Freedenberg, Ph.D., APRN, for “Psychosocial and biological effects of mindfulness-based stress reduction intervention in adolescents with CHD/CIEDs: a randomized control trial”
Renee’ Roberts Turner for “Peak and nadir experiences of mid-level nurse leaders”

2019-2020 Global Health Initiative Exploration in Global Health Awards
Nathalie Quion, M.D., for “Latino youth and families need assessment,” conducted in Washington
Sonia Voleti for “Handheld ultrasound machine task shifting,” conducted in Micronesia
Tania Ahluwalia, M.D., for “Simulation curriculum for emergency medicine,” conducted in India
Yvonne Yui for “Designated resuscitation teams in NICUs,” conducted in Ghana
Xiaoyan Song, Ph.D., MBBS, MSc, “Prevention of hospital-onset infections in PICUs,” conducted in China

Ninth Annual Research and Education Week Poster Session Awards

Basic and Translational Science
Faculty: Adeline (Wei Li) Koay, MBBS, MSc, for “Differences in the gut microbiome of HIV-infected versus HIV-exposed, uninfected infants”
Faculty: Hayk Barseghyan, Ph.D., for “Composite de novo Armenian human genome assembly and haplotyping via optical mapping and ultra-long read sequencing”
Staff: Damon K. McCullough, BS, for “Brain slicer: 3D-printed tissue processing tool for pediatric neuroscience research”
Staff: Antonio R. Porras, Ph.D., for “Integrated deep-learning method for genetic syndrome screening using facial photographs”
Post docs/fellows/residents: Lung Lau, M.D., for “A novel, sprayable and bio-absorbable sealant for wound dressings”
Post docs/fellows/residents: Kelsey F. Sugrue, Ph.D., for “HECTD1 is required for growth of the myocardium secondary to placental insufficiency”
Graduate students: Erin R. Bonner, BA, for “Comprehensive mutation profiling of pediatric diffuse midline gliomas using liquid biopsy”
High school/undergraduate students: Ali Sarhan for “Parental somato-gonadal mosaic genetic variants are a source of recurrent risk for de novo disorders and parental health concerns: a systematic review of the literature and meta-analysis”

Clinical Research
Faculty: Amy Hont, M.D., for “Ex vivo expanded multi-tumor antigen specific T-cells for the treatment of solid tumors”
Faculty: Lauren McLaughlin, M.D., for “EBV/LMP-specific T-cells maintain remissions of T- and B-cell EBV lymphomas after allogeneic bone marrow transplantation”

Staff: Iman A. Abdikarim, BA, for “Timing of allergenic food introduction among African American and Caucasian children with food allergy in the FORWARD study”
Staff: Gelina M. Sani, BS, for “Quantifying hematopoietic stem cells towards in utero gene therapy for treatment of sickle cell disease in fetal cord blood”
Post docs/fellows/residents: Amy H. Jones, M.D., for “To trach or not trach: exploration of parental conflict, regret and impacts on quality of life in tracheostomy decision-making”
Graduate students: Alyssa Dewyer, BS, for “Telemedicine support of cardiac care in Northern Uganda: leveraging hand-held echocardiography and task-shifting”
Graduate students: Natalie Pudalov, BA, “Cortical thickness asymmetries in MRI-abnormal pediatric epilepsy patients: a potential metric for surgery outcome”
High school/undergraduate students: Kia Yoshinaga for “Time to rhythm detection during pediatric cardiac arrest in a pediatric emergency department”

Community-Based Research
Faculty: Adeline (Wei Li) Koay, MBBS, MSc, for “Recent trends in the prevention of mother-to-child transmission (PMTCT) of HIV in the Washington, D.C., metropolitan area”
Staff: Gia M. Badolato, MPH, for “STI screening in an urban ED based on chief complaint”
Post docs/fellows/residents: Christina P. Ho, M.D., for “Pediatric urinary tract infection resistance patterns in the Washington, D.C., metropolitan area”
Graduate students: Noushine Sadeghi, BS, “Racial/ethnic disparities in receipt of sexual health services among adolescent females”

Education, Training and Program Development
Faculty: Cara Lichtenstein, M.D., MPH, for “Using a community bus trip to increase knowledge of health disparities”
Staff: Iana Y. Clarence, MPH, for “TEACHing residents to address child poverty: an innovative multimodal curriculum”
Post docs/fellows/residents: Johanna Kaufman, M.D., for “Inpatient consultation in pediatrics: a learning tool to improve communication”
High school/undergraduate students: Brett E. Pearson for “Analysis of unanticipated problems in CNMC human subjects research studies and implications for process improvement”

Quality and Performance Improvement
Faculty: Vicki Freedenberg, Ph.D., APRN, for “Implementing a mindfulness-based stress reduction curriculum in a congenital heart disease program”
Staff: Caleb Griffith, MPH, for “Assessing the sustainability of point-of-care HIV screening of adolescents in pediatric emergency departments”
Post docs/fellows/residents: Rebecca S. Zee, M.D., Ph.D., for “Implementation of the Accelerated Care of Torsion (ACT) pathway: a quality improvement initiative for testicular torsion”
Graduate students: Alysia Wiener, BS, for “Latency period in image-guided needle bone biopsy in children: a single center experience”

View images from the REW2019 award ceremony.

Beth Tarini

Getting to know SPR’s future President, Beth Tarini, M.D., MS

Beth Tarini

Quick. Name four pillar pediatric organizations on the vanguard of advancing pediatric research.

Most researchers and clinicians can rattle off the names of the Academic Pediatric Association, the American Academy of Pediatrics and the American Pediatric Society. But that fourth one, the Society for Pediatric Research (SPR), is a little trickier. While many know SPR, a lot of research-clinicians simply do not.

Over the next few years, Beth A. Tarini, M.D., MS, will make it her personal mission to ensure that more pediatric researchers get to know SPR and are so excited about the organization that they become active members. In May 2019 Dr. Tarini becomes Vice President of the society that aims to stitch together an international network of interdisciplinary researchers to improve kids’ health. Four-year SPR leadership terms begin with Vice President before transitioning to President-Elect, President and Past-President, each for one year.

Dr. Tarini says she looks forward to working with other SPR leaders to find ways to build more productive, collaborative professional networks among faculty, especially emerging junior faculty. “Facilitating ways to network for research and professional reasons across pediatric research is vital – albeit easier said than done. I have been told I’m a connector, so I hope to leverage that skill in this new role,” says Dr. Tarini, associate director for Children’s Center for Translational Research.

“I’m delighted that Dr. Tarini was elected to this leadership position, and I am impressed by her vision of improving SPR’s outreach efforts,” says Mark Batshaw, M.D., Executive Vice President, Chief Academic Officer and Physician-in-Chief at Children’s National. “Her goal of engaging potential members in networking through a variety of ways – face-to-face as well as leveraging digital platforms like Twitter, Facebook and LinkedIn – and her focus on engaging junior faculty will help strengthen SPR membership in the near term and long term.”

Dr. Tarini adds: “Success to me would be leaving after four years with more faculty – especially junior faculty – approaching membership in SPR with the knowledge and enthusiasm that they bring to membership in other pediatric societies.”

SPR requires that its members not simply conduct research, but move the needle in their chosen discipline. In her research, Dr. Tarini has focused on ensuring that population-based newborn screening programs function efficiently and effectively with fewer hiccups at any place along the process.

Thanks to a heel stick to draw blood, an oxygen measurement, and a hearing test, U.S. babies are screened for select inherited health conditions, expediting treatment for infants and reducing the chances they’ll experience long-term health consequences.

“The complexity of this program that is able to test nearly all 4 million babies in the U.S. each year is nothing short of astounding. You have to know the child is born – anywhere in the state – and then between 24 and 48 hours of birth you have to do testing onsite, obtain a specific type of blood sample, send the blood sample to an off-site lab quickly, test the sample, find the child if the test is out of range, get the child evaluated and tested for the condition, then send them for treatment. Given the time pressures as well as the coordination of numerous people and organizations, the fact that this happens routinely is amazing. And like any complex process, there is always room for improvement,” she says.

Dr. Tarini’s research efforts have focused on those process improvements.

As just one example, the Advisory Committee on Heritable Disorders in Newborns and Children, a federal advisory committee on which she serves, was discussing how to eliminate delays in specimen processing to provide speedier results to families. One possible solution floated was to open labs all seven days, rather than just five days a week. Dr. Tarini advocated for partnering with health care engineers who could help model ways to make the specimen transport process more efficient, just like airlines and mail delivery services. A more efficient and effective solution was to match the specimen pick-up and delivery times more closely with the lab’s operational times – which maximizes lab resources and shortens wait times for parents.

Conceptual modeling comes so easily for her that she often leaps out of her seat mid-sentence, underscoring a point by jotting thoughts on a white board, doing it so often that her pens have run dry.

“It’s like a bus schedule: You want to find a bus that not only takes you to your destination but gets you there on time,” she says.

Dr. Tarini’s current observational study looks for opportunities to improve how parents in Minnesota and Iowa are given out-of-range newborn screening test results – especially false positives – and how that experience might shake their confidence in their child’s health as well as heighten their own stress level.

“After a false positive test result, are there parents who walk away from newborn screening with lingering stress about their child’s health? Can we predict who those parents might be and help them?” she asks.

Among the challenges is the newborn screening occurs so quickly after delivery that some emotionally and physically exhausted parents may not remember it was done. Then they get a call from the state with ominous results. Another challenge is standardizing communication approaches across dozens of birthing centers and hospitals.

“We know parents are concerned after receiving a false positive result, and some worry their infant remains vulnerable,” she says. “Can we change how we communicate – not just what we say, but how we say it – to alleviate those concerns?”

Nickie Andescavage

To understand the preterm brain, start with the fetal brain

Nickie Andescavage

“My best advice to future clinician-scientists is to stay curious and open-minded; I doubt I could have predicted my current research interest or described the path between the study of early oligodendrocyte maturation to in vivo placental development, but each experience along the way – both academic and clinical – has led me to where I am today,” Nickie Andescavage, M.D., writes.

Too often, medical institutions erect an artificial boundary between caring for the developing fetus inside the womb and caring for the newborn whose critical brain development continues outside the womb.

“To improve neonatal outcomes, we must transform our current clinical paradigms to begin treatment in the intrauterine period and continue care through the perinatal transition through strong collaborations with obstetricians and fetal-medicine specialists,” writes Nickie Andescavage, M.D., an attending in Neonatal-Perinatal Medicine at Children’s National.

Dr. Andescavage’s commentary was published online March 25, 2019, in Pediatrics Research and accompanies recently published Children’s research about differences in placental development in the setting of placental insufficiency. Her commentary is part of a new effort by Nature Publishing Group to spotlight research contributions from early career investigators.

The placenta, an organ shared by a pregnant woman and the developing fetus, plays a critical but underappreciated role in the infant’s overall health. Under the mentorship of Catherine Limperopoulos, Ph.D., director of MRI Research of the Developing Brain, and Adré J. du Plessis, M.B.Ch.B., MPH, chief of the Division of Fetal and Transitional Medicine, Dr. Andescavage works with interdisciplinary research teams at Children’s National to help expand that evidence base.

While attending Cornell University as an undergraduate, Dr. Andescavage had an early interest in neuroscience and neurobehavior. As she continued her education by attending medical school at Columbia University, she corroborated an early instinct to work in pediatrics.

It wasn’t until the New Jersey native began pediatric residency at Children’s National that those complementary interests coalesced into a focus on brain autoregulation and autonomic function in full-term and preterm infants and imaging the brains of both groups. In normal, healthy babies the autonomic nervous system regulates heart rate, blood pressure, digestion, breathing and other involuntary activities. When these essential controls go awry, babies can struggle to survive and thrive.

“My best advice to future clinician-scientists is to stay curious and open-minded; I doubt I could have predicted my current research interest or described the path between the study of early oligodendrocyte maturation to in vivo placental development, but each experience along the way – both academic and clinical – has led me to where I am today,” Dr. Andescavage writes in the commentary.

ACC19 attendees from Children's National

ACC.19: A focus on pediatric cardiology

ACC19 attendees from Children's National

Dr. Gerard Martin, center, accepts an award before delivering the 2019 Dan G. McNamara Keynote lecture at ACC.19.

“Innovation meets tradition,” is how many attendees and journalists described the American College of Cardiology’s 68th Scientific Sessions (ACC.19), which took place March 16-18, 2019 in New Orleans, La.

Gerard Martin, M.D., F.A.A.P., F.A.C.C., F.A.H.A., a pediatric cardiologist and the medical director of Global Services at Children’s National, supported this narrative by referencing both themes in his 2019 Dan G. McNamara keynote lecture, entitled “Improved Outcomes in Congenital Heart Disease through Advocacy and Collaboration.” Dr. Martin highlighted advancements in the field of pediatric cardiology that took place over the past 15 years, while touting modern advancements – such as pulse oximetry screenings for critical congenital heart disease – that were a result of physician-led advocacy and collaboration.

Dr. Martin’s message was to continue to invest in research and technology that leads to medical breakthroughs, but to remember the power of partnerships, such as those formed by the National Pediatric Cardiology Quality Improvement Collaborative. These alliances, which generated shared protocols and infrastructure among health systems, improved interstage mortality rates between surgeries for babies born with hypoplastic left heart syndrome.

A dozen cardiologists and clinicians from the Children’s National Heart Institute also participated in CME panel discussions or delivered poster presentations to support future versions of this template, touching on early-stage innovations and multi-institution research collaborations. The themes among Children’s National Heart Institute faculty, presented to a diverse crowd of 12,000-plus professional attendees representing 108 countries, included:

Personalized guidelines:

  • Sarah Clauss, M.D., F.A.C.C., a cardiologist, presented “Unique Pediatric Differences from Adult Cholesterol Guidelines: Lipids and Preventive Cardiology,” before Charles Berul, M.D., division chief of cardiology and co-director of the Children’s National Heart Institute, presented “Unique Pediatric Differences from Adult Guidelines: Arrhythmias in Adults with Congenital Heart Disease,” in a joint symposium with the American Heart Association and the American College of Cardiology.
  • Berul, who specializes in electrophysiology, co-chaired a congenital heart disease pathway session, entitled “Rhythm and Blues: Electrophysiology Progress and Controversies in Congenital Heart Disease,” featuring components of pediatric electrophysiology, including heart block, surgical treatment of arrhythmias and sudden death risk.

Early detection:

  • Anita Krishnan, M.D., associate director of the echocardiography lab, presented “Identifying Socioeconomic and Geographic Barriers to Prenatal Detection of Hypoplastic Left Heart Syndrome and Transposition of the Great Arteries” as a moderated poster in Fetal Cardiology: Quickening Discoveries.
  • Jennifer Romanowicz, M.D., a cardiology fellow, and Russell Cross, M.D., director of cardiac MRI, presented the “Neonatal Supraventricular Tachycardia as a Presentation of Critical Aortic Coarctation” poster in FIT Clinical Decision Making: Congenital Heart Disease 2.
  • Pranava Sinha, M.D., a cardiac surgeon, presented the poster “Neuroprotective Effects of Vitamin D Supplementation in Children with Cyanotic Heart Defects: Insights from a Rodent Hypoxia Model” in Congenital Heart Disease: Therapy 2.

Coordinated care:

  • Ashraf Harahsheh, M.D., F.A.C.C., F.A.A.P., a cardiologist with a focus on hyperlipidemia and preventive cardiology, co-presented an update about BMI quality improvement (Q1) activity from the American College of Cardiology’s Adult Congenital and Pediatric Quality Network – BMI Q1 leadership panel.
  • Niti Dham, M.D., director of the cardio-oncology program, and Deepa Mokshagundam, M.D., cardiology fellow, presented the poster “Cardiac Changes in Pediatric Cancer Survivors” in Heart Failure and Cardiomyopathies: Clinical 3.
  • Nancy Klein, B.S.N., R.N., C.P.N., clinical program coordinator of the Washington Adult Congenital Heart program at Children’s National, presented the poster “Improving Completion of Advanced Directives in Adults with Congenital Heart Disease” in Risks and Rewards in Adult Congenital Heart Disease.

Innovation:

  • Jai Nahar, M.D., a cardiologist, moderated “Future Hub: Augmented Cardiovascular Practitioner: Giving Doctors and Patients a New Voice.” The session focused on technical aspects of artificial intelligence, such as language processing and conversational artificial intelligence, as well as how applications are used in patient-physician interactions.
  • Nahar also participated in a key event on the Heart-to-Heart stage, entitled “Rise of Intelligent Machines: The Potential of Artificial Intelligence in Cardiovascular Care.”

“While I enjoyed the significant representation of Children’s National faculty at the meeting and all of the presentations this year, one research finding that I found particularly compelling was Dr. Krishnan’s poster about geographical disparities in detecting congenital heart disease,” says Dr. Berul. “Her research finds obstetricians providing care to women in the lowest quartile of socioeconomic areas were twice as likely to miss a diagnosis for a critical congenital heart defect during a fetal ultrasound, compared to obstetricians providing care for women in the highest quartiles.”

Dr. Krishnan’s study was the collaborative effort of 21 centers in the United States and Canada, and investigated how socioeconomic and geographic factors affect prenatal detection of hypoplastic left heart syndrome and transposition of the great arteries.

“We studied over 1,800 patients, and chose these diseases because they require early stabilization by a specialized team at a tertiary care center,” says Dr. Krishnan, who led the research in conjunction with the Fetal Heart Society Research Collaborative. “We hope that by understanding what the barriers are, we can reduce disparities in care through education and community-based outreach.”

Dr. Kurt Newman in front of the capitol building

Kurt Newman, M.D., shares journey as a pediatric surgeon in TEDx Talk

Kurt Newman, M.D., president and chief executive officer of Children’s National, shares his poignant journey as a pediatric surgeon, offering a new perspective for approaching the most chronic and debilitating health conditions. In this independently-organized TEDx event, Dr. Newman also shares his passion for Children’s National and the need to increase pediatric innovations in medicine.

Robin Steinhorn in the NICU

Coming together as a team for the good of the baby

Robin Steinhorn in the NICU

Children’s National has a new program to care for children who have severe bronchopulmonary dysplasia, a serious complication of preterm birth.

Around the 1-year-old’s crib is a tight circle of smiling adults, and at the foot of his bed is a menagerie of plush animals, each a different color and texture and shape to spark his curiosity and sharpen his intellect.

Gone are the days a newborn with extremely complex medical needs like Elijah would transfer from the neonatal intensive care unit (NICU) to the pediatric intensive care unit and transition through a couple of other hospital units by the time he was discharged. Gone are the days when he’d see a variety of new physician faces at every stop. And gone are the days he’d be confined to his room, divorced from the sights and sounds and scents of the outside world, stimulation that helps little baby’s neural networks grow stronger.

Children’s National has a new program designed to meet the unique needs of children like Elijah who have severe bronchopulmonary dysplasia (BPD), a common complication of preterm birth.

“It’s more forward-thinking – and I mean thinking for the future of each individual baby, and it’s allowing the baby to have one team and one location to take advantage of a deep knowledge of and relationship with that baby and family,” says Robin Steinhorn, M.D. Dr. Steinhorn is senior vice president of the Center for Hospital-Based Specialties and one of Children’s multidisciplinary team members who visited Elijah’s bed twice weekly during his lengthy hospitalization and who continues to see him regularly during outpatient visits.

“The pulmonologist, the neonatologist, the respiratory therapist, the physical therapist, the dietitian, the cardiologist – we all come as a team to work together for the good of the baby,” Dr. Steinhorn adds. “We stick with these babies through thick and thin. We will stick with that baby with this team and this location until they are ready to go home – and beyond.”

BPD, a serious lung condition, mostly affects extremely low birthweight preterm babies whose lungs were designed to continue developing inside the womb until the pregnancy reaches full term. Often born months before their due dates, these extremely vulnerable newborns have immature organs, including the lungs, which are not ready for the task of breathing air. Children’s program targets infants who experience respiratory failure from BPD. The respiratory support required for these infants ranges from oxygen delivered through a nasal cannula to mechanical ventilators.

Robin Steinhorn and Colleague

“It’s more forward-thinking – and I mean thinking for the future of each individual baby, and it’s allowing the baby to have one team and one location to take advantage of a deep knowledge of and relationship with that baby and family,” says Robin Steinhorn, M.D.

About 1 percent of all preterm births are extremely low birthweight, or less than 1,500 grams. Within that group, up to 40 percent will develop BPD. While they represent a small percentage of overall births, these very sick babies need comprehensive, focused care for the first few years of their lives. And some infants with severe BPD also have pulmonary hypertension which, at Children’s National, is co-managed by cardiology and pulmonary specialists.

Children’s BPD team not only focuses on the child’s survival and medical care, they focus on the neurodevelopmental and social care that a baby needs to thrive. From enhanced nutrition to occupational and physical therapy to a regular sleep cycle, the goal is to help these babies achieve their full potential.

“These babies are at tremendous risk for long-term developmental issues. Everything we do is geared to alleviate that,” adds John T. Berger III, M.D., director of Children’s Pulmonary Hypertension Program.

“Our NICU care is more focused, comprehensive and consistent,” agrees Mariam Said, M.D., a neonatologist on the team. “We’re also optimizing the timing of care and diagnostic testing that will directly impact health outcomes.”

Leaving no detail overlooked, the team also ensures that infants have age-appropriate developmental stimuli, like toys, and push for early mobility by getting children up and out of bed and into a chair or riding in a wagon.

“The standard approach is to keep the baby in a room with limited physical or occupational therapy and a lack of appropriate stimulation,” says Geovanny Perez, M.D., a pulmonologist on the team. “A normal baby interacts with their environment inside the home and outside the home. We aim to mimic that within the hospital environment.”

Dr. Steinhorn, who had long dreamed of creating this comprehensive team care approach adds that “it’s been so gratifying to see it adopted and embraced so quickly by Children’s NICU caregivers.”

Prescription for a healthy heart: pediatric-driven partnerships

Dr. Martin and a patient share a smile after a visit at Children’s National Health System.

For pediatric cardiologists, February, National Heart Month, is a special time. We share health tips in the hospital and talk about heart health with those looking for advice, especially with patients and families impacted by congenital heart disease (CHD). It’s also a time to look back at what’s worked well in the field, while accelerating advancements for CHD treatment.

To start, congenital heart disease, a structural abnormality of the heart or of the blood vessels surrounding it, is the most common birth defect and occurs in about one in every 100 live births, affecting 40,000 babies born in the U.S. each year. One million children and 1.4 million adults in the U.S. have CHD. Over the past 15 years, pediatric cardiologists have cut mortality rates for CHD in half. Gratefully, now instead of saving children’s lives, the emphasis is on improving them. The catalyst for this paradigm shift isn’t simply due to a medical breakthrough, but is also the result of collaboration and advocacy.

Pediatric cardiologists worked together with other stakeholders – nurses, neonatologists, parents, state and federal agencies – to implement newborn screening methods in hospitals, with the introduction pulse oximetry screenings for critical congenital heart defects (CCHD). The screening, which measures blood oxygen levels in newborns, focuses on screening babies for CCHD before they leave the hospital. The concept and a national protocol for screening began with a small project in 2002, was endorsed by medical associations by 2012 and required by all states in 2018. The impact of CCHD screening of newborns is remarkable. Data published in JAMA showed a 33 percent reduction in CCHD infant deaths associated with states that required CCHD screening.

The pulse oximetry screening’s impact on the number of lives saved goes beyond identifying newborns with CCHD. Worldwide, though the detection of secondary conditions, such as hypothermia, pneumonia, and sepsis, the pulse oximetry screening is estimated to save roughly 772,000 lives by 2030.

In addition to newborn screening recommendations for CCHD, a group of cardiologists, including myself, worked for the Joint Council on Congenital Heart Disease (JCCHD) to form and support the National Pediatric Cardiology Quality Improvement Collaborative (NPC-QIC). We developed measures to see how we could improve survival rates between surgeries for infants born with hypoplastic left heart syndrome (HLHS), one of the most common and severe forms of CCHD.

Babies born with HLHS require two heart surgeries within the baby’s first six months. Babies that survived the first operation had a significant mortality rate (15 percent) and frequent growth failure, while waiting for the second operation. Our focused aims were to both decrease the death rate and improve growth in these children. We analyzed data from medical centers, utilized quality improvement principals from the Institute for Health Care Improvement, talked with doctors and families, and invited teams from across the U.S. to partner with us to put quality and safety measures into place.

We emphasized the following points:

  1. Clear communication. Parents leaving the hospital received consistent messages about CHD, the type of surgery their baby had, next steps and how to care for their child at home.
  2. Improved nutrient intake. Parents received clear guidelines about how many calories babies needed to consume, were asked to weigh their baby each day, and taught how to augment feeding.
  3. Warning signs.Parents received a list of typical infant behaviors and HLHS red flags to watch out for, such as if a baby isn’t gaining a certain amount of weight. They received monitors to measure oxygen saturation levels at home. If oxygen saturation dropped significantly or if parents noticed a problem, they called their doctor immediately.

The implementation of these procedures reduced interstage mortality rates and the number of growth failures for HLHS patients. In 2008, six centers participated in the NPC-QIC pilot. By 2018, 65 medical centers in the U.S. and Canada used these methods. Similar to the pulse oximetry screening guidelines, this new method wasn’t the result of a medical breakthrough, but the result of shared learning and shared infrastructure.

Now, we’re referring more adult congenital heart patients to board-certified adult congenital heart disease (ACHD) specialists, a better fit than internists or pediatric cardiologists. Adults with congenital heart defects should have their heart examined at least once by a specialist and those with complex needs should meet with a specialist at least every two years. More than 300 board-certified ACHD specialists practice in the U.S. and the field is growing. The third ACHD board exam takes place this year.

Over the next few decades, I hope we’ll make even more progress with understanding, diagnosing and treating CHD.

Emerging research examines genetic clues for congenital heart defects, which were once thought to account for 8 percent of cases and may now account for 30 percent of conditions. We’re working with neurologists to examine the timing and pathway of potential oxygen inefficiencies that occur as the brain develops in utero, infancy, and after neonatal surgery. We’ve come a long way, but we continue looking at new frontiers and for innovative solutions.

Fortunately, as cardiologists, we’re good at fixing problems. We work with surgeons and medical teams to repair holes in hearts, or replace them, and reroute blood from an underdeveloped left ventricle to improve circulation. For almost every heart defect, we have evidence-based solutions. However, to continue to help children worldwide, it’s imperative that we don’t forget about what works well: good science, tracking data, sharing best practices, active listening, transparency and constant collaboration.

Gerard Martin, M.D., F.A.A.P., F.A.C.C., F.A.H.A., is a cardiologist and the medical director of global services at Children’s National Health System. Dr. Martin has practiced pediatric cardiology for 34 years and is the Dan G. McNamara keynote speaker at the American College of Cardiology’s 2019 Scientific Sessions. Follow Dr. Martin on Twitter @Gerard_MD.

This article first appeared on KevinMD.com.

heart and medical equiptment

How much do you know about congenital heart defects?


Nikki Gillum Posnack

What are the health effects of plastics?

Nikki Gillum Posnack

Nikki Posnack, Ph.D., assistant professor at the Children’s National Heart Institute, is an early-stage investigator examining the impact plastic chemical exposure has on the developing hearts of newborns and young children.

For newborns or children in the pediatric intensive care unit, plastic tubing is part of daily life. It delivers life-sustaining blood transfusions, liquid nutrition and air to breathe. But small amounts of the chemicals in the plastic of this tubing and other medical devices can leak into the patient’s bloodstream. The potential effects of these chemicals on the developing hearts of newborns and very young children are not well understood.

One researcher, Nikki Posnack, Ph.D., an assistant professor at the Children’s National Heart Institute, aims to change that and shares her early insights, funded by the National Center for Advancing Translation Science (NCATS), in an NCATS news feature.

“While plastics have revolutionized the medical field, we know chemicals in plastics leach into the body and may have unintended effects,” Posnack said. “The heart is sensitive to toxins, so we want to look at the effect of these plastics on the most sensitive patient population: kids who are recovering from heart surgery and already prone to cardiac complications.”

Dr. Bear Bot

Advances in telemedicine start with new cardiac critical care robot

Dr. Bear Bot

Dr. Bear Bot’s “robot-only” parking space in the Cardiac ICU. Alejandro Lopez-Magallon, M.D., is featured on the robot display screen, where he drives the robot from his location in the command center, in order to visit patient rooms and capture additional medical information and connect with patients, parents, and attending nurses and physicians.

The telemedicine robot at Children’s National arrived in late August 2018 and recently completed a 90-day test period in the tele-cardiac intensive care unit (cardiac ICU) at Children’s National. The bot travels between rooms as a virtual liaison connecting patients and attending nurses and physicians with Ricardo Munoz, M.D., executive director of the telemedicine program and the division chief of critical cardiac care, and Alejandro Lopez-Magallon, M.D., a cardiologist and medical director of the telemedicine program.

Drs. Munoz and Lopez-Magallon use a nine-screen virtual command center to remotely monitor patient vitals, especially for infants and children who are recovering from congenital heart surgery, flown in for an emergency diagnostic procedure, such as a catheterization, or who are in the process of receiving a heart or kidney transplant. Instead of traveling to individual rooms to check in on the status of one patient, the doctors can now monitor multiple patients simultaneously, enhancing their ability to diagnose, care for and intervene during critical events.

If Drs. Munoz or Lopez-Magallon need to take an X-ray or further examine a patient, they drive the robot from its ‘robot-only’ parking space adjacent to the nurse’s station, and connect with attending doctors and nurses in the teaming area. The onsite clinicians accompany one of the telemedicine doctors, both of whom remain in the command center but appear virtually on the robot’s display screen, to the patient’s room to capture additional medical information and to connect with patients and families.

Over time, the telemedicine team will measure models of efficiency in the tele-cardiac ICU, such as through-put, care coordination, and standards of safety, quality and care, measured by quality of life and short- and long-term patient health outcomes. This test run will serve as a model for future command centers offering remote critical care.

Ricardo Munoz and Alejandro Lopez-Magallon

(R) Ricardo Munoz, M.D., executive director of the telemedicine program and the division chief of critical cardiac care, and Alejandro Lopez-Magallon, M.D., a cardiologist and the associate medical director of the telemedicine program in the tele-cardiac ICU command center.

“As technology and medicine advance, so do our models of telemedicine, which we call virtual care,” says Shireen Atabaki, M.D., M.P.H., an emergency medicine physician at Children’s National, who manages an ambulatory virtual health program, which enables patients to use virtual health platforms to connect with doctors, but from the comfort of their home. “We find the patient-centered platforms and this new technology saves families’ time and we’re looking forward to studying internal models to see how this can help our doctors, enabling us to do even more.”

The ongoing virtual connection program that Dr. Atabaki references launched in spring 2016 and has enabled 900 children to connect to a doctor from a computer, tablet or smart phone, which has saved families 1,600 driving hours and more than 41,000 miles over a two-year period. Through this program, virtual care is provided to children in our region by 20 subspecialists, including cardiologists, dermatologists, neurologists, urgent care doctors, geneticists, gastroenterologists and endocrinologists.

To extend the benefits of virtual communication, while saving mileage and time, Dr. Atabaki and the telemedicine team at Children’s National will partner with K-12 school systems, local hospitals and health centers and global health systems.

The Children’s National robot was named Dr. Bear Bot after a 21-day voting period with patients and staff, beating 14 other child-selected names, including SMARTy (Special Medical Access to Remote Technology), Dr. Bot and Rosie. Dr. Bear Bot celebrated with an official reveal party on Valentine’s Day, which was streamed to over 220 patients through the hospital’s closed-circuit television and radio station.

dystrophin protein

Experimental drug shows promise for slowing cardiac disease and inflammation

dystrophin protein

Duchenne muscular dystrophy (DMD) is caused by mutations in the DMD gene, which provides instructions for making dystrophin, a protein found mostly in skeletal, respiratory and heart muscles.

Vamorolone, an experimental medicine under development, appears to combine the beneficial effects of prednisone and eplerenone – standard treatments for Duchenne muscular dystrophy (DMD) – in the heart and muscles, while also showing improved safety in experimental models. The drug does so by simultaneously targeting two nuclear receptors important in regulating inflammation and cardiomyopathy, indicates a small study published online Feb. 11, 2019, in Life Science Alliance.

DMD is a progressive X-linked disease that occurs mostly in males. It is characterized by muscle weakness that worsens over time, and most kids with DMD will use wheelchairs by the time they’re teenagers. DMD is caused by mutations in the DMD gene, which provides instructions for making dystrophin, a protein found mostly in skeletal, respiratory and heart muscles.

Cardiomyopathy, an umbrella term for diseases that weaken the heart, is a leading cause of death for young adults with DMD, causing up to 50 percent of deaths in patients who lack dystrophin. A collaborative research team co-led by Christopher R. Heier, Ph.D., and Christopher F. Spurney, M.D., of Children’s National Health System, is investigating cardiomyopathy in DMD. They find genetic dystrophin loss provides “a second hit” for a specific pathway that worsens cardiomyopathy in experimental models of DMD.

“Some drugs can interact with both the mineralocorticoid receptor (MR) and glucocorticoid receptor (GR) since these two drug targets evolved from a common ancestor. However, we find these two drug targets can play distinctly different roles in heart and skeletal muscle. The GR regulates muscle inflammation, while the MR plays a key role in heart health,” says Heier, an assistant professor at Children’s National and lead study author. “In our study, the experimental drug vamorolone safely targets both the GR to treat chronic inflammation and the MR to treat the heart.”

After gauging the efficacy of various treatments in test tubes, the study team looked at whether any could mitigate negative impacts of the MR on heart health. Wild type and mdx experimental models were implanted with pumps that activated the MR. These models also received a daily oral MR antagonist (or inhibitor) drug, and either eplerenone, spironolactone or vamorolone. Of note:

  • MR activation increased kidney size and caused elevated blood pressure (hypertension).
  • Treatment with vamorolone maintained normal kidney size and prevented hypertension.
  • MR activation increased mdx heart mass and fibrosis. Vamorolone mitigated these changes.
  • MR activation decreased mdx heart function, while vamorolone prevented declines in function.
  • Daily prednisone caused negative MR- and GR-mediated side effects, such as hyperinsulinemia, whereas vamorolone safely improved heart function without these side effects.

“These findings have the potential to help current and future patients,” Heier says. “Clinicians already prescribe several of these drugs. Our new data support the use of MR antagonists such as eplerenone in protecting DMD hearts, particularly if patients take prednisone. The experimental drug vamorolone is currently in Phase IIb clinical trials and is particularly exciting for its unique potential to simultaneously treat chronic inflammation and heart pathology with improved safety.”

In addition to Heier and senior author Spurney, study co-authors include Qing Yu, Alyson A. Fiorillo, Christopher B. Tully, Asya Tucker and Davi A. Mazala, all of Children’s National; Kitipong Uaesoontrachoon and Sadish Srinivassane, AGADA Biosciences Inc.; and Jesse M. Damsker, Eric P. Hoffman and Kanneboyina Nagaraju, ReveraGen BioPharma.

Financial support for research described in this report was provided by Action Duchenne; the Clark Charitable Foundation; the Department of Defense under award W81XWH-17-1-047; the Foundation to Eradicate Duchenne; the Intellectual and Developmental Disabilities Research Center under award U54HD090257 (through the National Institutes of Health’s (NIH) Eunice Kennedy Shriver National Institute of Child Health and Human Development); and the NIH under awards K99HL130035, R00HL130035, L40AR068727 and T32AR056993.

Financial disclosure:  Co-authors employed by ReveraGen BioPharma were involved in creating this news release.

mitochondria

Treating nephrotic-range proteinuria with tacrolimus in MTP

mitochondria

Mitochondria are the cell’s powerplants and inside them the MTP enzymatic complex catalyzes three steps in beta-oxidation of long-chain fatty acids.

In one family, genetic lightning struck twice. Two sisters were diagnosed with mitochondrial trifunctional protein (MTP) deficiency. This is a rare condition that stops the body from converting fats to energy, which can lead to lactic acidosis, recurrent breakdown of muscle tissue and release into the bloodstream (rhabdomyolysis), enlarged heart (cardiomyopathy) and liver failure.

Mitochondria are the cell’s powerplants and inside them the MTP enzymatic complex catalyzes three steps in beta-oxidation of long-chain fatty acids. MTP deficiency is so rare that fewer than 100 cases have been reported in the literature says Hostensia Beng, M.D., who presented an MTP case study during the American Society of Nephrology’s Kidney Week.

The 7-month-old girl with known MTP deficiency arrived at Children’s National lethargic with poor appetite. Her laboratory results showed a low corrected serum calcium level, elevated CK level and protein in the urine (proteinuria) at a nephrotic range. The infant was treated for primary hypoparathyroidism and rhabdomyolysis.

Even though the rhabdomyolysis got better, the excess protein in the girl’s urine remained at worrisome levels. A renal biopsy showed minimal change disease and foot process fusion. And electron microscopy revealed shrunken, dense mitochondria in visceral epithelial cells and endothelium.

“We gave her tacrolimus, a calcineurin inhibitor that we are well familiar with because we use it after transplants to ensure patient’s bodies don’t reject the donated organ. By eight months after treatment, the girl’s urine protein-to-creatinine (uPCR) ratio was back to normal. At 35 months, that key uPCR measure rose again when tacrolimus was discontinued. When treatment began again, uPCR was restored to normal levels one month later,” Dr. Beng says.

The girl’s older sister also shares the heterozygous deletion in the HADHB gene, which provides instructions for making MTP. That missing section of the genetic how-to guide was predicted to cause truncation and loss of long-chain-3-hydroxyacl CoA dehydrogenase function leading to MTP deficiency.

The older sister was diagnosed with nephrotic syndrome and having scar tissue in the kidney’s filtering unit (focal segmental glomerulosclerosis) when she was 18 months old. By contrast, she developed renal failure and progressed to end stage renal disease at 20 months of age.

“Renal involvement has been reported in only one patient with MTP deficiency to date, the older sister of our patient,” Dr. Beng adds.

Podocytes are specialized cells in the kidneys that provide a barrier, preventing plasma proteins from leaking into the urine. Podocytes, however, need energy to function and are rich in mitochondria.

“The proteinuria in these two sisters may be related to their mitochondrial dysfunction. Calcineurin inhibitors like tacrolimus have been reported to reduce proteinuria by stabilizing the podocyte actin cytoskeleton. Tacrolimus was an effective treatment for our patient, who has maintained normal renal function, unlike her sister,” Dr. Beng says.

American Society of Nephrology’s Kidney Week presentation

  • “Treatment of nephrotic-range proteinuria with tacrolimus in mitochondrial trifunctional protein deficiency

Hostensia Beng, M.D., lead author; Asha Moudgil, M.D., medical director, transplant, and co-author; Sun-Young Ahn, M.D., MS, medical director, nephrology inpatient services, and senior author, all of Children’s National Health System.

E coli bacteria

Urinary bacteria in spinal cord injury cases may tip balance toward UTIs

E coli bacteria

Patients with spinal cord injuries nearly universally have bacteria present in their urine regardless of whether they have a urinary tract infection.

The fallout from spinal cord injury doesn’t end with loss of mobility: Patients can have a range of other issues resulting from this complex problem, including loss of bladder control that can lead to urine retention. One of the most serious implications is urinary tract infections (UTIs), the most common cause of repeat hospitalization in people with spinal cord injuries, explains Hans G. Pohl, M.D., associate chief in the division of Urology at Children’s National Health System.

Diagnosing UTIs in people with spinal cord injuries is trickier than in people who are otherwise healthy, Dr. Pohl explains. Patients with spinal cord injuries nearly universally have bacteria present in their urine regardless of whether they have a UTI. It’s unclear whether these bacteria are innocent bystanders or precursors to UTIs in patients who don’t yet show symptoms. And although antibiotics can wipe out this bacterial population, these drugs can have undesirable side effects and frequent use can promote development of antibiotic-resistant bacteria.

Although clinical dogma has long promoted the idea that “healthy” urine is sterile, Dr. Pohl and colleagues have shown that a variety of bacteria live in urine, even in people without symptoms. These microorganisms, like the intestinal microbiome, live in harmony with their hosts and may even help promote health. However, it’s unclear what this urinary microbiome might look like for patients with spinal cord injury before, during and after UTIs.

To start investigating this question, Dr. Pohl and co-authors recently reported a case study they published online Sept. 21, 2018, in Spinal Cord Series and Cases. The case report about a 55-year-old man who had injured the thoracic segment of his spinal cord—about the level of the bottom of his shoulder blades—in a skiing accident when he was 19 was selected as “Editor’s Choice” for the journal’s October 2018 issue.  The patient had a neurogenic bladder, which doesn’t function normally due to impaired communication with the spinal cord. To compensate for this loss of function, this patient needed to have urine removed every four to six hours by catheterization.

Over eight months Dr. Pohl, the study’s senior author, and colleagues collected 12 urine samples from this patient:

  • One was collected at a time the patient didn’t show any symptoms of a UTI
  • Nine were collected when the patient had UTI symptoms, such as bladder spasticity
  • Two samples were collected when the patient had finished antibiotic treatment for the UTI.

The researchers split each sample in half. One part was put through a standard urinalysis and culture, much like what patients with a suspected UTI would receive at the doctor’s office. The other part was analyzed using a technique that searched for genetic material to identify bacteria that might be present and to estimate their abundance.

The researchers found a variety of different bacteria present in these urine samples. Regardless of the patient’s health status and symptoms, the majority of these bacterial species are known to be pathogenic or potentially pathogenic. By contrast, this patient’s urine microbiome appeared to largely lack bacterial species known to be either neutral or with potentially probiotic properties, such as Lactobacillus.

All of the bacteria that grew in culture also were identified by their genetic material in the samples. However, genetic sequencing also identified a possible novel uropathogenic species called Burkholderia fungorum that didn’t grow in the lab in five of the samples. This bacterium is ubiquitous in the environment and has been identified in soil- and plant-based samples. It also has been discovered in the respiratory secretions of patients with cystic fibrosis, in patients with a heart condition called infectious endocarditis, in the vaginal microbiota of patients with bacterial vaginosis, and in the gut of patients with HIV who have low T-cell counts. Dr. Pohl says it’s unclear whether this species played an infectious role in this patient’s UTI or whether it’s just part of his normal urine flora.

“Consistent with our previous work, this case report demonstrates that rather than healthy urine being sterile, there is a diverse urine bacterial ecosystem during various states of health and disease,” Dr. Pohl says. “Rather than UTIs resulting from the growth or overgrowth of a single organism, it’s more likely that a change in the healthy balance of the urine ecosystem might cause these infections.”

By monitoring the relative abundance of different bacteria types present in the urine of patients with spinal cord injury and combining this information with a patient’s symptoms, Dr. Pohl says doctors may be able to make more accurate UTI diagnoses in this unique population.

In addition to Dr. Pohl, study co-authors include Marcos Pérez-Losada, Ljubica Caldovic, Ph.D., Bruce Sprague and Michael H. Hsieh, M.D., Children’s National; Emma Nally, Suzanne L. Groah and Inger Ljungberg, MedStar National Rehabilitation Hospital; and Neel J. Chandel, Montefiore Medical Center.

Nobuyuki Ishibashi

Cortical dysmaturation in congenital heart disease

Nobuyuki Ishibashi

On Jan. 4, 2019, Nobuyuki Ishibashi, M.D., the director of the Cardiac Surgery Research Laboratory and an investigator with the Center for Neuroscience Research at Children’s National Health System, published a review in Trends in Neurosciences about the mechanisms of cortical dysmaturation, or disturbances in cortical development, that can occur in children born with congenital heart disease (CHD). By understanding the early-life impact and relationship between cardiac abnormalities and cortical neuronal development, Dr. Ishibashi and the study authors hope to influence strategies for neonatal neuroprotection, mitigating the risk for developmental delays among CHD patients.

Dr. Ishibashi answers questions about this review and CHD-neurodevelopmental research:

  1. Tell us more about your research. Why did you choose to study these interactions in this patient population?

My research focuses on studying how CHD and neonatal cardiac surgery affect the rapidly-developing brain. Many children with CHD, particularly the most complex anomalies, suffer from important behavioral anomalies and neurodevelopmental delays after cardiac surgery. As a surgeon scientist, I want to optimize treatment strategy and develop a new standard of care that will reduce neurodevelopmental impairment in our patients.

  1. How does this study fit into your larger body of work? What are a few take-home messages from this paper?

Our team and other laboratories have recently identified a persistent perinatal neurogenesis that targets the frontal cortex – the brain area responsible for higher-order cognitive functions. The main message from this article is that further understanding of the cellular and molecular mechanisms underlying cortical development and dysmaturation will likely help to identify novel strategies to treat and improve outcomes in our patients suffering from intellectual and behavioral disabilities.

  1. What do you want pediatricians and researchers to know about this study? Why is it important right now?

Although the hospital mortality risk is greatly reduced, children with complex CHD frequently display subsequent neurological disabilities affecting intellectual function, memory, executive function, speech and language, gross and fine motor skills and visuospatial functions. In addition to the impact of the neurological morbidity on the patients themselves, the toll on families and society is immense. Therefore it is crucial to determine the causes of altered brain maturation in CHD.

  1. How do you envision this research influencing future studies and pediatric health outcomes? As a researcher, how will you proceed?

In this article we placed special emphasis on the need for well-designed preclinical studies to define disturbances in cortical neurogenesis due to perinatal brain injury. I believe that further study of the impact of hypoxemia on brain development is of broad relevance — not just for children with congenital heart disease, but for other populations where intellectual and behavioral dysfunctions are a source of chronic morbidity, such as survivors of premature birth.

  1. What discoveries do you envision being at the forefront of this field?

One of the important questions is: During which developmental period, prenatal or postnatal, is the brain most sensitive to developmental and behavioral disabilities associated with hypoxemia? Future experimental models will help us study key effects of congenital cortical development anomalies on brain development in children with CHD.

  1. What impact could this research make? What’s the most striking finding and how do you think it will influence the field?

Although cortical neurogenesis at fetal and adult stages has been widely studied, the development of the human frontal cortex during the perinatal period has only recently received greater attention as a result of new identification of ongoing postnatal neurogenesis in the region responsible for important intellectual and behavioral functions. Children’s National is very excited with the discoveries because it has opened new opportunities that may lead to regeneration and repair of the dysmature cortex. If researchers identify ways to restore endogenous neurogenic abilities after birth, the risk of neurodevelopment disabilities and limitations could be greatly reduced.

  1. Is there anything else you would like to add that we didn’t ask you about? What excites you about this research?

In this article we highlight an urgent need to create a truly translational area of research in CHD-induced brain injury through further exploration and integration of preclinical models. I’m very excited about the highly productive partnerships we developed within the Center for Neuroscience Research at Children’s National, led by an internationally-renowned developmental neuroscientist, Vittorio Gallo, Ph.D., who is a co-senior author of this article. Because of our collaboration, my team has successfully utilized sophisticated and cutting-edge neuroscience techniques to study brain development in children born with CHD. To determine the causes of altered brain maturation in congenital heart disease and ultimately improve neurological function, we believe that a strong unity between cardiovascular and neuroscience research must be established.

Additional study authors include Camille Leonetti, Ph.D., a postdoctoral research fellow with the Center for Neuroscience Research and Children’s National Heart Institute, and Stephen Back, M.D., Ph.D., a professor of pediatrics at Oregon Health and Science University.

The research was supported by multiple grants and awards from the National Institutes of Health, inclusive of the National Heart Lung and Blood Institute (RO1HL139712), the National Institute of Neurological Disorders and Stroke (1RO1NS054044, R37NS045737, R37NS109478), the National Institute on Aging (1RO1AG031892-01) and the National Institute of Child Health and Human Development (U54HD090257).

Additional support for this review was awarded by the American Heart Association (17GRNT33370058) and the District of Columbia Intellectual and Developmental Disabilities Research Center, which is supported through the Eunice Kennedy Shriver National Institute of Child Health and Human Development program grant 1U54HD090257.

AlgometRX

Breakthrough device objectively measures pain type, intensity and drug effects

AlgometRX

Clinical Research Assistant Kevin Jackson uses AlgometRx Platform Technology on Sarah Taylor’s eyes to measure her degree of pain. Children’s National is testing an experimental device that aims to measure pain according to how pupils react to certain stimuli. (AP Photo/Manuel Balce Ceneta)

Pediatric anesthesiologist Julia C. Finkel, M.D., of Children’s National Health System, gazed into the eyes of a newborn patient determined to find a better way to measure the effectiveness of pain treatment on one so tiny and unable to verbalize. Then she realized the answer was staring back at her.

Armed with the knowledge that pain and analgesic drugs produce an involuntary response from the pupil, Dr. Finkel developed AlgometRx, a first-of-its-kind handheld device that measures a patient’s pupillary response and, using proprietary algorithms, provides a diagnostic measurement of pain intensity, pain type and, after treatment is administered, monitors efficacy. Her initial goal was to improve the care of premature infants. She now has a device that can be used with children of any age and adults.

“Pain is very complex and it is currently the only vital sign that is not objectively measured,” says Dr. Finkel, who has more than 25 years of experience as a pain specialist. “The systematic problem we are facing today is that healthcare providers prescribe pain medicine based on subjective self-reporting, which can often be inaccurate, rather than based on an objective measure of pain type and intensity.” To illustrate her point, Dr. Finkel continues, “A clinician would never prescribe blood pressure medicine without first taking a patient’s blood pressure.”

The current standard of care for measuring pain is the 0-to-10 pain scale, which is based on subjective, observational and self-reporting techniques. Patients indicate their level of pain, with zero being no pain and ten being highest or most severe pain. This subjective system increases the likelihood of inaccuracy, with the problem being most acute with pediatric and non-verbal patients. Moreover, Dr. Finkel points out that subjective pain scores cannot be standardized, heightening the potential for misdiagnosis, over-treatment or under-treatment.

Dr. Finkel, who serves as director of Research and Development for Pain Medicine at the Sheikh Zayed Institute for Pediatric Surgical Innovation at Children’s National, says that a key step in addressing the opioid crisis is providing physicians with objective, real-time data on a patient’s pain level and type, to safely prescribe the right drug and dosage or an alternate treatment.,

She notes that opioids are prescribed for patients who report high pain scores and are sometimes prescribed in cases where they are not appropriate. Dr. Finkel points to the example of sciatica, a neuropathic pain sensation felt in the lower back, legs and buttocks. Sciatica pain is carried by touch fibers that do not have opioid receptors, which makes opioids an inappropriate choice for treating that type of pain.

A pain biomarker could rapidly advance both clinical practice and pain research, Dr. Finkel adds. For clinicians, the power to identify the type and magnitude of a patient’s nociception (detection of pain stimuli) would provide a much-needed scientific foundation for approaching pain treatment. Nociception could be monitored through the course of treatment so that dosing is targeted and personalized to ensure patients receive adequate pain relief while reducing side effects.

“A validated measure to show whether or not an opioid is indicated for a given patient could ease the health care system’s transition from overreliance on opioids to a more comprehensive and less harmful approach to pain management,” says Dr. Finkel.

She also notes that objective pain measurement can provide much needed help in validating complementary approaches to pain management, such as acupuncture, physical therapy, virtual reality and other non-pharmacological interventions.

Dr. Finkel’s technology, called AlgometRx, has been selected by the U.S. Food and Drug Administration (FDA) to participate in its “Innovation Challenge: Devices to Prevent and Treat Opioid Use Disorder.” She is also the recipient of Small Business Innovation Research (SBIR) grant from the National Institute on Drug Abuse.

Girl complaining to doctor about stitch in side

Treating children and teens with undiagnosed stomach problems?

Girl complaining to doctor about stitch in side

Children and teens exhibiting symptoms of orthostatic intolerance (OI) or gastrointestinal (GI) distress may benefit from a new diagnostic tool, pairing a tilt table test with manometry, which combines the two fields and can yield better results in some cases than testing for either symptom alone.

A combination of two diagnostic tools to test for cardiovascular and gastrointestinal function provides potential answers for patients left feeling sick and with inconclusive results.

Imagine you’re a pediatrician and see a teenage patient who complains of gastrointestinal (GI) distress: nausea, bloating and abdominal pain. She hasn’t altered her diet or taken new medications. An ultrasound of her internal organs from a radiologist comes back clear. You refer her to a gastroenterologist to see if her GI tract, a tube that runs from her mouth to the bottom of her stomach, and houses many organs, including the esophagus, intestines and stomach, has inflammation or structural anomalies. The symptoms, depending on the severity of the problem, could range from mildly irritating to intrusive, leading to missed days from work or school.

The gastroenterologist may analyze her GI tract with an endoscope and often takes a biopsy to look at a sample of the intestinal lining for lesions and inflammation. The results, like the ultrasound, may come back clear.

While an “all-clear” diagnosis is good news for patients awaiting the results of a test for a disease process, these results frustrate patients with chronic GI problems. Without a definitive diagnosis, these patients and their doctors often worry about ‘missing something’ and are left searching for solutions—and scheduling more tests.

Research published in The Journal of Pediatrics, entitled “Utility of Diagnostic Studies for Upper Gastrointestinal Symptoms in Children with Orthostatic Intolerance,” and discussed on Oct. 24 at the 2018 Single Topic Symposium at the Annual Meeting of the North American Society of Pediatric Gastroenterology, Hepatology and Nutrition (NASPGHAN), entitled Advances in Motility and in Neurogastroenterology (AIMING) for the future, now provides doctors with preliminary answers and a tool to test for orthostatic intolerance (OI).

The research team, a mix of cardiologists and gastroenterologists from Children’s National Health System, examined consecutive medical records of over 100 children and young adults with OI, a result of insufficient blood flow returning to the heart after standing up from a reclined position, which could result in lightheadedness or fainting, as well as gastrointestinal symptoms, including nausea and vomiting.

All patients had antroduodenal manometry, a test that uses a catheter, placed during an upper GI endoscopy, to measure the motility of the stomach and of the upper small intestines, in conjunction with a tilt-table test to measure blood pressure and heart rate changes with a change in posture. A gastric emptying study (GES) was performed in about 80 percent of the patients. The study found that antroduodenal manometry combined with the tilt-table test provided the best insights into adolescents and young adults with OI and GI symptoms.

Anil Darbari, M.D., MBA, a study author and the director of the comprehensive GI motility program at Children’s National, mentions the research highlights advances in the field of GI motility. It provides insights into the underlying pathophysiology of the conditions affecting the function of the GI tract and a roadmap to offer a multidisciplinary approach to help patients with sensory or motor GI motility problems, including those with OI or postural orthostatic tachycardia syndrome (POTS).

According to the National Institutes of Health, POTS is a form of OI, which affects more than 500,000 Americans, and most cases are diagnosed in women between the ages of 15 and 50. The cause of POTS is unknown but may begin after major surgery, trauma, a viral illness, pregnancy or before menstruation. The goal of treatment is to improve circulation and alleviate associated symptoms, including blurred vision, headaches, shortness of breath, weakness, coldness or pain in the extremities and GI symptoms, such as nausea, cramps and vomiting.

Dr. Darbari mentions that when his team and other GI motility doctors see patients for predominant GI symptoms, the patients may be frustrated because their primary GI providers often cannot find anything  wrong with their GI tracts— based on the routine testing including laboratory studies, radiological tests and endoscopy with biopsy, at least that they can find. Dr. Darbari isn’t surprised since the symptoms of GI distress and POTS often overlap. Nausea is seen in up to 86 percent of OI patients, a number similar to lightheadedness, which affects 87 percent of OI or POTS patients.

“The physicians and GI specialists are frustrated because they can’t find anything wrong so they think the patient is making up these symptoms,” says Dr. Darbari. “It’s a dichotomous relationship between the patient and physician because of the traditional tests, which almost always come back normal. This is where the field of neurogastroenterology or GI motility comes in. We’re able to explain what’s happening based on the function or motility of the GI tract.”

Dr. Darbari mentions that combining these two fields—testing for cardiovascular function and GI motility—provides the science behind these sought-out answers. The problem, and pain that patients feel affects the neuro-gastro part of the intestine, as opposed to appearing as inflammation, lesions or structural damage.

When asked about how this research may change the field of gastroenterology, Dr. Darbari explains that it’s important to continue to study the underlying mechanisms that control these symptoms. More research, especially from the basic science point of view, is needed to look at how the nerves interact with the muscles. He hopes that scientists will look at the nerve and how the nerve is laid out, as well as how the GI function interacts with that of the cardiovascular system.

Understanding this relationship will help gastroenterologists better understand how to manage these conditions. Right now the solutions involve integrative therapy, such as prescribing sensory modulation, which could include pain management, behavior modification, massage therapy, aroma therapy, acupuncture, meditation and/or hypnotherapy, in addition to or in place of medications to decrease sensory perception in the GI tract. The treatment varies for each patient.

The prospect of giving families answers, and continuing to guide treatment based on the best science, is also what motivates Lindsay Clarke, PA-C, a study author and the coordinator of the GI Motility program at Children’s National, to continue to search for solutions.

“I spend a lot of time on the phone with these families between appointments, between visits, and between procedures,” says Clarke. “They have seen other gastroenterologists. They have had GI testing. Nothing comes back to show why they are feeling this way. This research gives them real information. We can now say that your symptoms are real. We’ve found the connection between what you’re feeling and what’s going on inside of your body.”

“It’s a huge quality-of-life issue for these patients,” adds Dr. Darbari about the benefits of having data to guide treatment. “These are often well-appearing kids. People, including medical professionals, often brush off their symptoms because the patients look good. They don’t have lesions or any redness or swelling, compared, for example, to patients with inflammatory bowel disease, who appear unwell or who have clear physical, laboratory and radiological findings. They don’t appear to be broken.”

The study authors note patient dissatisfaction, health care provider frustration, high costs of care and potentially hazardous diagnostic studies often accompany endoscopic and radiologic studies that fail to reveal significant abnormalities.

Clarke envisions that the use of the dual tilt-table test and antroduodenal manometry may also encourage families to explore multidisciplinary treatment earlier on in a patient’s life, such as physical therapy or sensory therapy, to alleviate symptoms and the overall number of outpatient visits. It provides them the understanding to enroll in a multidisciplinary and comprehensive programs, and programs that offer complementary therapies for management of these complex symptoms.

“This study shows that it’s important to look beyond individual organs and to treat the whole child,” says Clarke. “We’re still not sure about which kinds of sensory therapies work best and we don’t want to overstate the aims of integrative treatments, especially since it may vary for each child, but as clinicians we’re looking forward to talking to families about potential solutions, cautiously, as the science unfolds.”

Additional study authors include Lana Zhang, M.D., Jeffrey Moak, M.D., Sridhar Hanumanthaiah, M.B.B.S., and Robin Fabian, R.N., from the Division of Cardiology at Children’s National, John Desbiens, B.S., from the Division of Gastroenterology at Children’s National, and Rashmi D. Sahay, M.D., from the Division of Biostatistics and Epidemiology at Cincinnati Children’s Hospital Medical Center.

Photo of nurses in the cardiac intensive care unit at Children's National

Can pyruvate support metabolic function following heart surgery?

Photo of nurses in the cardiac intensive care unit at Children's National

Nurses rush a child to the cardiac intensive care unit at Children’s National Health System.

Can pyruvate, the end product of glycolysis, help improve cardiovascular function in children who have cardiopulmonary bypass surgery and suffer from low cardiac output syndrome (LCOS)? This question is one that Rafael Jaimes, Ph.D., a staff scientist at Children’s National Heart Institute, a division of Children’s National Health System, is studying, thanks to a two-year grant from the American Heart Association.

The competitive grant awards Dr. Jaimes with $110,000 to study how pyruvate may help improve cardiac output among pediatric patients with LCOS. The compound aims to stimulate metabolic function, now treated by inotropic agents, such as dobutamine and milrinone. These agents ensure optimal delivery of oxygen from the heart to the brain, as well as to other organs in the body, following heart surgery. While these agents help patients with cardiac dysfunction, there is still a critical need for safe and effective therapies.

“If there’s any detriment in cardiac output, the heart’s function begins to degrade,” explains Dr. Jaimes. “You see a downward spiral effect with reduced cardiac output because the heart is dependent on its own perfusion. It needs to pump blood throughout the body to survive.”

This is where the pyruvate study, and the grant, will be applied: Can pyruvate target the essential muscle of the heart and reverse this cardiac destabilization – and as soon as possible?

“By increasing the metabolic output of the heart’s local muscle, cardiac output increases,” Dr. Jaimes explains. “That’s going to lead to better recovery.”

Better recovery could be measured by how fast a child recovers from heart surgery as well as how much time they spend in the hospital, clinically referred to as throughput. A faster recovery could also influence a child’s quality of life and reduce overall health care costs.

Based on preliminary data that shows pyruvate improves cardiac function in experimental models after ischemic insult, which is what happens when pediatric patients undergo cardiac surgery, Dr. Jaimes believes the results will likely replicate themselves in his preclinical models.

To start, he’ll test pyruvate using 100 blood samples and discarded tissue from patients. The blood samples will be tested for metabolic markers, including measured pyruvate levels.

Part of what encouraged Dr. Jaimes to study how this compound could complement or replace standard therapies was the encouragement he received from his mentors in the field.

“Nobody has looked into using pyruvate for almost 30 years,” says Dr. Jaimes. “It’s not commercially favorable, there’s no patent on it, it doesn’t have a lot of marketability and there are no financial incentives, so it’s been put aside.”

As part of a discussion with cardiologists at a medical conference in Washington, Dr. Jaimes brought up the idea of using pyruvate for pediatric heart surgeries and received positive feedback.

“Once everyone’s eyes lit up, I knew I was on to something,” says Dr. Jaimes about the encouragement he received to pursue this study.

“You put lactate and glucose in your IV solutions,” adds Dr. Jaimes. “Pyruvate is an essential nutrient. It’s almost an essential sugar so there’s no reason not to put it in. If these cardiologists are intrigued by the project, maybe the American Heart Association will be, too.”

In addition to funding the study, which could support future research about how metabolic makers in the blood can be stimulated to fast-track recovery following heart surgery, the American Heart Association grant is specific to pediatric health outcomes.

“The current state of pharmaceutical treatment for patients recovering from cardiac surgery is designed and created for adults,” says Dr. Jaimes. “From our research in pediatrics, we know that children aren’t small adults.”

Dr. Jaimes explains that children are different on an anatomical and physiological level. Their cells even look and function different, compared to adult cells, because they haven’t matured yet.

While congenital heart defects are rare, they affect 1 percent, or 40,000 births worldwide, they often require multiple surgeries throughout a child’s lifespan. LCOS impacts 25 percent of patients following cardiopulmonary bypass and the timing of treatment is important. In severe cases, insufficient cardiac output following surgery could impact a child’s long-term development, ranging from reasoning, learning, attention and executive function, to developing age-appropriate language and social skills.

“The metabolic insufficiencies I’m looking at, which may help improve the muscle function of the heart, are just one piece of a bigger puzzle in pediatric cardiology,” notes Dr. Jaimes about ongoing research at Children’s National Heart Institute. “We already know pyruvate is safe. We just have to see if it’s effective in supporting a patient’s recovery in the intensive care unit.”

Dr. Jaimes will work with his research mentor Nikki Posnack, Ph.D., assistant professor at the Children’s National Heart Institute, on this preclinical study throughout the grant’s lifecycle, which starts in early January 2019 and ends in late December 2020.

Shriprasad Deshpande

Accelerating advanced cardiac treatments for tiny patients

Shriprasad Deshpande

Shriprasad Deshpande, M.B.B.S., M.S., a pediatric cardiologist, joins Children’s National Health System as the director of the advanced cardiac therapies and heart transplant program.

Shriprasad Deshpande, M.B.B.S., M.S., a pediatric cardiologist, has joined Children’s National Health System as the director of the advanced cardiac therapies and heart transplant program.

Dr. Deshpande, an intensivist and heart failure and transplant cardiologist, will work within the Children’s National Heart Institute (the Division of Cardiology and the Division of Cardiac Intensive Care) to guide the diagnosis and treatment of pediatric heart failure. He will also work with researchers, surgeons and engineers to accelerate the field of biomedical research and make it easy for patients to receive advanced therapies, such as mechanical pumps to support circulation, and, if necessary, heart transplant.

“Subspecializing in personalized care is critical for all patients right now, not just adults,” says Dr. Deshpande. “This is one of the reasons I’m looking forward to working with Children’s National, a leader in the many subdivisions of pediatric medicine and research.

“Our priority is to recognize the special needs of infants and children as they relate to heart failure,” he adds. “We want to provide the best care and advance science at the same time.”

As an example, a grant from the National Institutes of Health enabled Dr. Deshpande to test ventricular assist devices for infants. Through another NIH grant, he analyzed the safety of organ transplants by testing a donor’s DNA, instead of conducting invasive biopsies in children.

“The field of cardiology is in a unique position now to take advantage of discoveries happening in science, technology and engineering,” says Dr. Deshpande. “In addition to thinking about the logistics of heart transplants, we’re thinking about how we can delay the need for a heart transplant, understand how to grow tissue better and utilize technology to improve these outcomes. We’re investing in a child’s quality of life.”

As the medical director of Mechanical Circulatory Support Program at Children’s Healthcare of Atlanta, Dr. Deshpande led the mechanical circulatory support program and created a subspecialty clinic to provide treatment for pediatric heart failure patients. He started the Muscular Dystrophy Cardiomyopathy clinic, which analyzes and treats cardiovascular comorbidities associated with muscular dystrophy. While he was an assistant professor of pediatrics at Emory University School of Medicine, he created a curriculum for pediatric cardiologists and for nurses training in the cardiac intensive critical care unit.

Dr. Deshpande has published more than 70 studies and abstracts and will oversee clinical practice models, subspecialty clinics and academic research efforts at Children’s. His current research portfolio, inclusive of grants from the NIH and other funding agencies, is robust and varied: He’s studying how to improve mechanical support for complex heart disease patients, how to improve the performance of current pumps and how to develop new algorithms for these devices. Improving the diagnosis of transplant rejection, using technology to improve compliance and using new technologies to diagnose rejection, without invasive biopsies, are his other research interests.

Dr. Deshpande serves as the chair of the scientific committee at the nonprofit Enduring Hearts and is on the American Heart Association’s Strategically Focused Research Network committee.

Asha Moudgil examines a young patient

Preventing cardiovascular disease after pediatric kidney transplant

Asha Moudgil examines a young patient

Pediatric nephrologist Asha Moudgil, M.D. examines a kidney transplant patient.

As obesity has continued to rise among children in the U.S., so has a condition called metabolic syndrome – a constellation of factors, including high abdominal fat, insulin resistance, high blood pressure, high triglycerides and low amounts of high-density lipoprotein (“good” cholesterol), that increase future risk of cardiovascular disease.

Although metabolic syndrome is dangerous in otherwise healthy children, it’s particularly so for those who’ve received kidney transplants due to chronic kidney disease, says pediatric nephrologist Asha Moudgil, M.D., medical director of transplant at Children’s National Health System. Dr. Moudgil and Children’s National co-authors, Registered Dietitian Kristen Sgambat, Ph.D., RD, and Cardiologist Sarah Clauss, M.D., published a literature review in the February 2018 Clinical Kidney Journal outlining recent research about the cardiovascular effects of metabolic syndrome after kidney transplantation.

“Simply having this transplant multiplies the risk of cardiovascular disease in this vulnerable population,” Dr. Moudgil says. “Combined with lifestyle factors that are driving up metabolic syndrome in general, it’s a ‘one-two punch’ for these patients.”

Dr. Moudgil explains that chronic kidney disease itself leads to poor growth, resulting in shorter stature that’s a risk factor for developing increased waist-to-height ratio upon becoming overweight. When children with this condition undergo long-awaited transplants, it reverses some factors that were suppressing appetite and keeping weight in check: The chronically high levels of urea in their blood decrease after transplant, improving their appetites; and there’s no need to maintain the restrictive diets they had been required to follow for kidney health prior to transplant.

The pharmaceutical regimen that patients follow post-transplant often includes steroids that independently contribute to weight gain and insulin resistance. Combined with the typical American high-fat, high-sugar, and high-sodium diet and low levels of physical activity, the majority of patients with chronic kidney disease gain significant weight after they receive transplants. The prevalence of obesity doubles the first year after transplantation, from about 15 percent to 30 percent, not only driving up cardiovascular disease risk but endangering the longevity of their transplant.

At the same time, says Sgambat, risk factors before and after transplantation drive up prevalence of other parts of metabolic syndrome. These include hypertension, which affects the majority of patients with chronic kidney disease before transplant and typically worsens due to sodium and water retention from immunosuppressive drugs. Dyslipidemia, or abnormal lipid concentrations in the blood, is also common among pediatric kidney transplant patients. One study included in the review showed that 71 percent of patients had high triglycerides three months post-transplant.

Ethnicity also can drive up risk for metabolic syndrome and cardiovascular disease. For example, the literature review says, individuals of African descent have a higher risk of these two conditions potentially due to genetic factors, such as high risk apolipoprotein L1 gene variants.

Together, these factors spur production of inflammatory molecules that trigger the development of early cardiovascular disease. Many kidney transplant recipients die from cardiovascular complications in early adulthood, Sgambat says, driving the need for early detection.

To that end, Dr. Moudgil says pediatric patients don’t typically show overt abnormalities in standard measures of cardiac functioning, such as echocardiography. As an alternative, she and colleagues cover three tools in the literature review that could offer advanced insight into whether patients have initial signs of cardiovascular disease. One of these is carotid intima-media thickness, a measure of the thickness of the carotid artery that can be obtained noninvasively by ultrasound. Another is myocardial strain imaging by speckle tracking echocardiography, a global measure of how the heart changes shape while beating. Cardiac magnetic resonance imaging (MRI), a relatively new technique, is already showing promise in detecting signs of early cardiovascular dysfunction.

A far simpler way to gauge cardiovascular risk, Sgambat adds, is calculating patients’ waist-to-height ratio. This measure doesn’t require sophisticated tools and can be tracked in any clinic over time, alerting patients to health-altering changes before it’s too late.

“It’s even more important to treat cardiovascular risk factors aggressively in this population,” Sgambat says. “Getting a concrete measure that something is trending in the wrong direction may motivate patients to change their diet or lifestyle in ways that a simple recommendation may not.”

Craig Sable

Can a vaccine prevent the earliest forms of rheumatic heart disease?

Craig Sable

Craig Sable, M.D., associate chief of the division of cardiology and director of echocardiography at Children’s National Health System, earned a lifetime achievement award, formally known as the 2018 Cardiovascular Disease in the Young (CVDY) Meritorious Achievement Award, on Nov. 10 at the American Heart Association’s Scientific Sessions 2018.

The CVDY Council bestows the prestigious award to individuals making a significant impact in the field of cardiovascular disease in the young. The CVDY Council supports the mission to improve the health of children and adults with congenital heart disease and acquired heart disease during childhood through research, education, prevention and advocacy.

Dr. Sable is recognized for his entire body of research, education and advocacy focused on congenital and acquired heart disease, but especially for his rheumatic heart disease (RHD) research in Uganda.

Over the past 15 years, Dr. Sable has brought more than 100 doctors and medical staff to Kampala, the capital and largest city in Uganda, partnering with more than 100 local doctors and clinicians to develop a template for a sustainable infrastructure to diagnose, treat and prevent both RHD and congenital heart disease.

RHD is a result of damage to the heart valves after acute rheumatic fever (ARF). The process starts with a sore throat from streptococcal infection, which many children in the United States treat with antibiotics.

“For patients who develop strep throat, their body’s reaction to the strep throat, in addition to resolving its primary symptoms, can result in attacking the heart,” says Dr. Sable. “The initial damage is called acute rheumatic fever. In many cases this disease is self-limited, but if undetected, over years, it can lead to long-term heart valve damage called rheumatic heart disease. Unfortunately, once severe RHD develops the only treatment is open-heart surgery.”

In 2017, Sable and the researchers published a study in the New England Journal of Medicine about the global burden of RHD, which is often referred to as a disease of poverty.

RHD is observed more frequently in low- and middle-income countries as well as in marginalized communities in high-income countries. RHD has declined on a global scale, but it remains the most significant cause of morbidity and mortality from heart disease in children and young adults throughout the world.

In 2017 there were 39.4 million causes of RHD, which resulted in 285,000 deaths and 9.4 million disability-adjusted life-years.

In 2018 the World Health Organization issued a referendum recognizing rheumatic heart disease as an important disease that member states and ministries of health need to prioritize in their public health efforts.

The common denominator that drives Dr. Sable and the global researchers, many of whom have received grants from the American Heart Association to study RHD, is the impact that creating a scalable solution, such as widespread adoption of vaccines, can have on entire communities.

“The cost of an open-heart surgery in Uganda is $5,000 to $10,000, while treatment for a child with penicillin for one year costs less than $1,” says Dr. Sable. “Investment in prevention strategies holds the best promise on a large scale to eradicate rheumatic heart disease.”

Sable and the team have screened more than 100,000 children and are conducting the first randomized controlled RHD trial, enrolling nearly 1,000 children, to examine the effectiveness of using penicillin to prevent progression of latent or subclinical heart disease, the earliest form of RHD.

During the Thanksgiving holiday weekend, Dr. Sable and a team of surgeons will fly back to Uganda to operate on children affected by RHD, while also advancing their research efforts to produce a scalable solution, exported on a global scale, to prevent RHD in its earliest stages.

Dr. Sable and colleagues from around the world partner on several grant-funded research projects. Over the next few years, the team hopes to answer several important questions, including: Does penicillin prevent the earliest form of RHD and can we develop a vaccine to prevent RHD?

To view the team’s previously-published research, visit Sable’s PubMed profile.

To learn about global health initiatives led by researchers at Children’s National, visit www.GHICN.org.