Cardiology & Heart Surgery

Pregnant-Mom

Safeguarding fetal brain health in pregnancies complicated by CHD

Pregnant-Mom

During the last few weeks of pregnancy, certain regions of the fetal brain experience exponential growth but also are more vulnerable to injury during that high-growth period.

Yao Wu, Ph.D., a research postdoctoral fellow in the Developing Brain Research Laboratory at Children’s National Health System, has received a Thrasher Research Fund early career award to expand knowledge about regions of the fetal brain that are vulnerable to injury from congenital heart disease (CHD) during pregnancy.

CHD, the most common birth defect, can have lasting effects, including overall health issues; difficulty achieving milestones such as crawling, walking or running; and missed days at daycare or school, according to the Centers for Disease Control and Prevention. Brain injury is a major complication for infants born with CHD. Catherine Limperopoulos, Ph.D., director of Children’s brain imaging lab, was the first to provide in vivo evidence that fetal brain growth and metabolism in the third trimester of pregnancy is impaired within the womb.

“It remains unclear which specific regions of the fetal brain are more vulnerable to these insults in utero,” Limperopoulos says. “We first need to identify early brain abnormalities attributed to CHD and understand their impact on infants’ later behavioral and cognitive development in order to better counsel parents and effectively intervene during the prenatal period to safeguard brain health.”

During the last few weeks of pregnancy, certain regions of the fetal brain experience exponential growth but also are more vulnerable to injury during that high-growth period. The grant, $26,749 over two years, will underwrite “Brain Development in Fetuses With Congenital Heart Disease,” research that enables Wu to utilize quantitative, non-invasive magnetic resonance imaging (MRI) to compare fetal brain development in pregnancies complicated by CHD with brain development in healthy fetuses of the same gestational age.Wu will leverage quantitative, in vivo 3-D volumetric MRI to compare overall fetal and neonatal brain growth as well as growth in key regions including cortical grey matter, white matter, deep grey matter, lateral ventricles, external cerebrospinal fluid, cerebellum, brain stem, amygdala and the hippocampus.

The research is an offshoot of a prospective study funded by the National Institutes of Health that uses advanced imaging techniques to record brain growth in 50 fetuses in pregnancies complicated by CHD who need open heart surgery and 50 healthy fetuses. MRI studies are conducted during the second trimester (24 to 28 weeks gestational age), third trimester (33 to 37 weeks gestational age) and shortly after birth but before surgery. In addition, fetal and neonatal MRI measurements will be correlated with validated scales that measure infants’ and toddlers’ overall development, behavior and social/emotional maturity.

“I am humbled to be selected for this prestigious award,” Wu says. “The findings from our ongoing work could be instrumental in identifying strategies for clinicians and care teams managing high-risk pregnancies to optimize fetal brain development and infants’ overall quality of life.”

Dr.-Jonas.-WSPCHS

Snapshot: The Sixth Scientific Meeting of the World Society for Pediatric and Congenital Heart Surgery

Dr.-Jonas.-WSPCHS

Dr. Richard Jonas shows surgical advancements using 3D heart models, which participants could bring back to their host institutions.

On July 22, 2018, more than 700 cardiac specialists met in Orlando, Fla. for the Sixth Scientific Meeting of the World Society for Pediatric and Congenital Heart Surgery (WSPCHS 2018).

The five-day conference hosted a mix of specialists, ranging from cardiothoracic surgeons, cardiologists and cardiac intensivists, to anesthesiologists, physician assistants and nurse practitioners, representing 49 countries and six continents.

To advance the vision of WSPCHS – that every child born with a congenital heart defect should have access to appropriate medical and surgical care – the conference was divided into eight tracks: cardiac surgery, cardiology, anesthesia, critical care, nursing, perfusion, administration and training.

Richard Jonas, M.D., outgoing president of WSPCHS and the division chief of cardiac surgery at Children’s National Health System, provided the outgoing presidential address, delivered the keynote lecture on Transposition of the Great Arteries (TGA) and guided a surgical skills lab with printed 3-D heart models.

Other speakers from Children’s National include:

  • Gil Wernovsky, M.D., a cardiac critical care specialist, presented on the complex physiology of TGA, as well as long-term consequences in survivors of neonatal heart surgery, including TGA and single ventricle.
  • Mary Donofrio, M.D., a cardiologist and director of the Fetal Heart Program, presented “Prenatal Diagnosis: Improving Accuracy and Planning Delivery for babies with TGA,” “Systemic Venous Abnormalities in the Fetus,” “Intervention for Fetal Lesions Causing High Output Heart Failure” and “Fetal Cardiac Care – Can We Improve Outcomes by Altering the Natural History of Disease?”
  • Gerard Martin, M.D., a cardiologist and medical director of global services, presented “Is the Arterial Switch as Good as We Thought It Would Be?” and “Impact, MAPIT, NCPQIC – How and Why We Should All Embrace Quality Metrics.”
  • Pranava Sinha, M.D., a cardiac surgeon, presented the abstract “Cryopreserved Valved Femoral Vein Homografts for Right Ventricular Outflow Tract Reconstruction in Infants.”

Participants left with knowledge about how to diagnose and treat complex congenital heart disease, and an understanding of the long-term consequences of surgical management into adulthood. In addition, they received training regarding standardized practice models, new strategies in telemedicine and collaborative, multi-institutional research.

“It was an amazing experience for me to bring my expertise to a conference which historically concentrated on surgical and interventional care and long-term follow-up,” says Dr. Donofrio. “The collaboration between the fetal and postnatal care teams including surgeons, interventionalists and intensive care doctors enables new strategies to be developed to care for babies with CHD before birth. Our hope is that by intervening when possible in utero and by planning for specialized care in the delivery room, we can improve outcomes for our most complex patients”.

The Johns Hopkins University School of Medicine, Florida Board of Nursing, American Academy of Nurse Practitioners National Certification Program, American Nurses Credentialing Center and the American Board of Cardiovascular Perfusion provided continuing medical credits for eligible providers.

“I was so proud to be a member of the Children’s National team at this international conference,” notes Dr. Wernovsky. “We had to the opportunity to share our experience in fetal cardiology, outpatient cardiology, cardiac critical care, cardiac nursing and cardiac surgery with a worldwide audience, including surgical trainees, senior cardiovascular surgeons and the rest of the team members necessary to optimally care for babies and children with complex CHD. In addition, members of the nursing staff shared their research about advancements in the field. It was quite a success – both for our team and for all of the participants.”

Washington Adult Congenital Heart Program staff

The Washington Adult Congenital Heart Program earns national accreditation from the Adult Congenital Heart Association

Washington Adult Congenital Heart Program staff

The Washington Adult Congenital Heart Program (WACH), part of Children’s National, earns accreditation from the Adult Congenital Heart Association for providing high-level, integrated care to patients with congenital heart disease.

Anitha John, M.D., Ph.D., a congenital heart disease (CHD) specialist and the director of the Washington Adult Congenital Heart Program (WACH) at Children’s National Health System, is a master of creating and leading multidisciplinary teams and networks to drive innovative standards to accelerate personalized treatment for adults born with heart conditions.

The Adult Congenital Heart Association (ACHA), a national organization dedicated to advancing adult congenital heart disease (ACHD) care, announces WACH as one of 19 medical centers in the country – and the first in the Mid-Atlantic region – to earn its accreditation, which signifies a center that provides high-level, comprehensive care.

WACH receives this accreditation by meeting ACHA’s criteria, which includes medical services and personnel requirements, and going through a rigorous accreditation process, both of which were developed over a number of years through a collaboration with doctors, physician assistants, nurse practitioners, nurses and ACHD patients.

There are 1.4 million adults in the U.S. living with one of many different types of congenital heart defects, ranging among simple, moderate and complex.

“There are now more adults than children in the U.S. with CHD,” said Mark Roeder, President and CEO of ACHA. “Accreditation will elevate the standard of care and have a positive impact on the futures of those living with this disease. Coordination of care is key, and this accreditation program will make care more streamlined for ACHD patients, improving their quality of life.”

A study published in Circulation examined mortality rates among 70,000 patients living with CHD over a 15-year period, from 1990 to 2005, and saw mortality rates fall with referrals to specialized ACHD care centers.

“This accreditation lets patients and other specialists know what to expect if they visit our center,” says Dr. John. “While the field of congenital heart disease is small enough to personalize, it’s large enough to standardize. I’m grateful to work with a wonderful team to provide this type of high-level care.”

Dr. John has a unique background to elevate standards of ACHD care, while creating tailored prescriptions. She is one of a handful of physicians with subspecialty training in ACHD, which she completed at the Mayo Clinic. Her formal training in internal medicine and general pediatrics, completed at Brown University, fits well with the subspecialty training she received as a pediatric cardiology fellow at Children’s Hospital of Philadelphia. Her research now focuses on clinical outcomes in congenital cardiology and advancing multicenter research efforts in adult congenital cardiology.

From March 2016 to 2018, Dr. John led the Alliance for Adult Research in Congenital Cardiology, the major multicenter research group in the U.S. focused on ACHD research. She’s also working with experts and patient advocates to guide efforts to set up a future ACHD patient registry, which will continue to guide research efforts and educate providers about ACHD care.

To help facilitate collaboration, Dr. John guides quarterly meetings of the Mid-Atlantic ACHD regional group.  Established in 2011 through Children’s National, the group has expanded to include ACHD providers from over 18 programs/practices from across the East Coast. This group provides a forum for patient case discussion and programmatic support. More importantly, the professional collaboration has served to not only improve patient care but also provides support to providers as they continue to care for a growing population of patients. This type of collaboration fosters mutual understanding and sets the stage for a relaxed but collegial environment where questions flow and learning occurs.

To further facilitate education, she created an inaugural patient day at the 7th Annual Adult Congenital Heart Disease in the 21st Century conference this past year, allowing patients to have their own educational summit – while opening the opportunity to providers to stay an extra day to learn about patient-centered care. The conference relies heavily on the participation of the Mid-Atlantic ACHD regional group of providers.

Patients learned as much about 3D heart models, pacemakers and noninvasive surgical techniques as they did about personalized approaches to lifestyle care, from practicing mindfulness to hearing about communication strategies to use with their medical teams and families. A variety of experts, from cardiac surgeons to clinical social workers, led the panels and breakout sessions.

“We’re empowering patients to become an active participant and an engaged member of their medical care team,” adds Dr. John.

ACHA supports WACH’s efforts and spoke at the conference, complementing its mission to serve and support the more than one million adults with CHD, their families and the medical community.

The WACH team includes not only Dr. John, but ACHD cardiologists Seiji Ito, M.D., and Tacy Downing, M.D.; Pranava Sinha, M.D., surgical director; Rachel Steury, R.N.P., advanced practitioner; Nancy Klein, R.N., clinical coordinator; Emily Stein, M.S.W., social worker; Whitney Osborne, M.P.H., clinical research coordinator, and Ruth Phillippi, M.S., program coordinator. The team works together seamlessly to fulfill the program mission of achieving clinical excellence, promoting research and providing education in the care of adults of with CHD.

For more information about WACH or to take advantage of resources for ACHD providers, please contact 202-821-6289 or visit www.ChildrensNational.org/WACH.

Graph showing magnesium reduces arrhythmia risk

Magnesium helps prevent postsurgical arrhythmias in pediatric patients

Graph showing magnesium reduces arrhythmia risk

Magnesium (Mg) helps reduce arrhythmias, irregular heart rhythms, in adults. It also helps alleviate the symptoms of postoperative atrial fibrillation, or AFib, which can lead to blood clots, stroke and heart failure. Can it help prevent postsurgical arrhythmias in pediatric patients with congenital heart disease?

New research from Children’s National Health System finds a 25- or 50-mg dose of Mg used during congenital heart surgery (CHS) helps prevent arrhythmias, especially junctional ectopic tachycardia (JET) and atrial tachycardia (AT), common arrhythmias following CHS, according to a study published in the August 2018 edition of The Journal of Thoracic and Cardiovascular Surgery.

To reach this conclusion, the researchers separated 1,871 CHS patients from Children’s National into three groups: a control group of 750 patients who had surgery without Mg, a group of 338 patients receiving a 25-mg /kg dose of Mg during surgery and a group of 783 patients receiving a 50-mg/kg dose of Mg during surgery. The data looked at CHS cases over eight years, from 2005 to 2013, to determine if Mg administration during surgery alleviates postoperative arrhythmias and if the amount, measured by a 25- or 50-mg/kg dose, makes a difference.

“This study, the first conducted in pediatric patients, finds administering magnesium during congenital heart surgery reduces the likelihood of postsurgical arrhythmias,” says Charles Berul, M.D., a study author and the chief of cardiology at Children’s National. “We don’t detect a dose-dependent relationship, which means a small or larger amount of magnesium is equally effective at preventing arrhythmias following surgery.”

The researchers found that up to one-third of CHS patients experience postoperative arrhythmias, with JET and AT accounting for more than two-thirds of arrhythmias following CHS. They note that despite the administration of Mg during surgery, there continues to be a high incidence of postoperative arrhythmias – affecting 18 percent or about one in five CHS patients.

“We hope this study guides future research to see if adding new or additional agents to magnesium eliminates, or further reduces, postoperative arrhythmias,” notes Dr. Berul. “For now, we’re happy to find an algorithm to put into practice and to share with other medical centers, as a way to help pediatric patients recover from congenital heart surgery—stronger, faster and with a reduced risk of complications.”

The researchers note that postoperative arrhythmias impact the recovery period of CHS, increase the duration of intubation and CICU stay and prolong hospital stay.

Making the grade: Children’s National is nation’s Top 5 children’s hospital

Children’s National rose in rankings to become the nation’s Top 5 children’s hospital according to the 2018-19 Best Children’s Hospitals Honor Roll released June 26, 2018, by U.S. News & World Report. Additionally, for the second straight year, Children’s Neonatology division led by Billie Lou Short, M.D., ranked No. 1 among 50 neonatal intensive care units ranked across the nation.

Children’s National also ranked in the Top 10 in six additional services:

For the eighth year running, Children’s National ranked in all 10 specialty services, which underscores its unwavering commitment to excellence, continuous quality improvement and unmatched pediatric expertise throughout the organization.

“It’s a distinct honor for Children’s physicians, nurses and employees to be recognized as the nation’s Top 5 pediatric hospital. Children’s National provides the nation’s best care for kids and our dedicated physicians, neonatologists, surgeons, neuroscientists and other specialists, nurses and other clinical support teams are the reason why,” says Kurt Newman, M.D., Children’s President and CEO. “All of the Children’s staff is committed to ensuring that our kids and families enjoy the very best health outcomes today and for the rest of their lives.”

The excellence of Children’s care is made possible by our research insights and clinical innovations. In addition to being named to the U.S. News Honor Roll, a distinction awarded to just 10 children’s centers around the nation, Children’s National is a two-time Magnet® designated hospital for excellence in nursing and is a Leapfrog Group Top Hospital. Children’s ranks seventh among pediatric hospitals in funding from the National Institutes of Health, with a combined $40 million in direct and indirect funding, and transfers the latest research insights from the bench to patients’ bedsides.

“The 10 pediatric centers on this year’s Best Children’s Hospitals Honor Roll deliver exceptional care across a range of specialties and deserve to be highlighted,” says Ben Harder, chief of health analysis at U.S. News. “Day after day, these hospitals provide state-of-the-art medical expertise to children with complex conditions. Their U.S. News’ rankings reflect their commitment to providing high-quality care.”

The 12th annual rankings recognize the top 50 pediatric facilities across the U.S. in 10 pediatric specialties: cancer, cardiology and heart surgery, diabetes and endocrinology, gastroenterology and gastrointestinal surgery, neonatology, nephrology, neurology and neurosurgery, orthopedics, pulmonology and urology. Hospitals received points for being ranked in a specialty, and higher-ranking hospitals receive more points. The Best Children’s Hospitals Honor Roll recognizes the 10 hospitals that received the most points overall.

This year’s rankings will be published in the U.S. News & World Report’s “Best Hospitals 2019” guidebook, available for purchase in late September.

Baby in the NICU

Getting to the heart of cardiac output

Baby in the NICU

To keep infants in the neonatal intensive care unit (NICU) as healthy as possible, it’s important to keep close tabs on their vital signs. During their NICU stay, most babies have continuous monitoring of their blood pressure, respiratory rate and blood oxygen saturation. And although continuous monitoring of heart rate is also typically standard, other information about heart function – such as cardiac output, a measure of how well the heart is pumping blood – remains a challenge to obtain in these vulnerable babies.

Clinical markers like blood pressure, heart rate and urine output are available, but they are indirect measures of cardiac output, how much blood the heart pumps per minute. Less invasive techniques, such as Doppler ultrasound, can be imprecise. Respiratory mass spectrometry or catheterization would provide more precision by directly calculating cardiac output but carry risks or are not feasible for neonates.

Clinicians at Children’s National Health System hypothesized that COstatus monitors could offer a way to directly measure cardiac output among neonates. The COstatus monitor – a minimally invasive way to measure hemodynamics – captures cardiac output, total end diastolic volume, active circulation volume and central blood volume.

The research team tested the approach by leveraging ultrasound dilution: Injecting saline, which has an ultrasound velocity of 1533m/second, slows the ultrasound velocity of blood from its normal rate of 1580m/second and produces a dilution curve.

“It is feasible to directly measure neonatal cardiac output by ultrasound dilution via the COstatus monitor in the first two weeks of life with no adverse events,” says Khodayar Rais-Bahrami, M.D., a Children’s neonatologist and senior author for the research presented during the Pediatric Academic Societies 2018 annual meeting. “When we took consecutive measurements, we saw very little variance in the parameters.”

The COstatus monitor uses an extracorporeal loop that is connected to arterial and venous catheters. The 12 neonates included in the study already had umbilical venous catheters as well as either a peripheral arterial line or umbilical arterial catheter. The infants ranged in weight from 0.72 to 3.74 kg and were born at 24 to 41.3 gestational weeks.

The infants’ cardiac output was measured 54 times from 1 to 13 days of life. Up to two measurement sessions occurred daily for a maximum of four days. The mean cardiac output was 0.43 L/minute with a mean cardiac index of 197mL/kg/minute.

Future research will describe normal cardiac output ranges for neonates as well as how these measurements evolve during the first week of life.

In addition to Dr. Rais-Bahrami, study co-authors include Simranjeet S. Sran, M.D., and Mariam Said, M.D., a Children’s neonatologist.

Nikki Gillum Posnack

Examining BPA’s impact on developing heart cells

Nikki Gillum Posnack

“We know that once this chemical enters the body, it can be bioactive and therefore can influence how heart cells function,” says Nikki Gillum Posnack, Ph.D. “This is the first study to look at the impact BPA exposure can have on heart cells that are still developing.”

More than 8 million pounds of bisphenol A (BPA), a common chemical used in manufacturing plastics, is produced each year for consumer goods and medical products. This endocrine disruptor reaches 90 percent of the population, and excessive exposure to BPA, e.g., plastic bottles, cash register receipts, and even deodorant, is associated with adverse cardiovascular events that range from heart arrhythmias and angina to atherosclerosis, the leading cause of death in the U.S.

To examine the impact BPA could have in children, researchers with Children’s National Heart Institute and the Sheikh Zayed Institute for Pediatric Surgical Innovation evaluated the short-term risks of BPA exposure in a preclinical setting. This experimental research finds developing heart cells respond to short-term BPA exposure with slowed heart rates, irregular heart rhythms and calcium instabilities.

While more research is needed to provide clinical recommendations, this preclinical model paves the way for future study designs to see if young patients exposed to BPA from medical devices or surgical procedures have adverse cardiac events and altered cardiac function.

“Existing research explores the impact endocrine disruptors, specifically BPA, have on adults and their cardiovascular and kidney function,” notes Nikki Gillum Posnack, Ph.D., a study author and assistant professor at Children’s National and The George Washington University. “We know that once this chemical enters the body, it can be bioactive and therefore can influence how heart cells function. This is the first study to look at the impact BPA exposure can have on heart cells that are still developing.”

The significance of this research is that plastics have revolutionized the way clinicians and surgeons treat young patients, especially patients with compromised immune or cardiac function.

Implications of Dr. Posnack’s future research may incentivize the development of alternative products used by medical device manufacturers and encourage the research community to study the impact of plastics on sensitive patient populations.

“It’s too early to tell how this research will impact the development of medical devices and equipment used in intensive care settings,” notes Dr. Posnack. “We do not want to interfere with clinical treatments, but, as scientists, we are curious about how medical products and materials can be improved. We are extending this research right now by examining the impact of short-term BPA exposure on human heart cells, which are developed from stem cells.”

This research, which appears as an online advance in Nature’s Scientific Reports, was supported by the National Institutes of Health under awards R00ES023477, RO1HL139472 and UL1TR000075, Children’s Research Institute and the Children’s National Heart Institute. NVIDIA Corporation provided GPUs, computational devices, for this study.

banner year

2017: A banner year for innovation at Children’s National

banner year

In 2017, clinicians and research faculty working at Children’s National Health System published more than 850 research articles about a wide array of topics. A multidisciplinary Children’s Research Institute review group selected the top 10 articles for the calendar year considering, among other factors, work published in high-impact academic journals.

“This year’s honorees showcase how our multidisciplinary institutes serve as vehicles to bring together Children’s specialists in cross-cutting research and clinical collaborations,” says Mark L. Batshaw, M.D., Physician-in-Chief and Chief Academic Officer at Children’s National. “We’re honored that the National Institutes of Health and other funders have provided millions in awards that help to ensure that these important research projects continue.”

The published papers explain research that includes using imaging to describe the topography of the developing brains of infants with congenital heart disease, how high levels of iron may contribute to neural tube defects and using an incisionless surgery method to successfully treat osteoid osteoma. The top 10 Children’s papers:

Read the complete list.

Dr. Batshaw’s announcement comes on the eve of Research and Education Week 2018 at Children’s National, a weeklong event that begins April 16, 2018. This year’s theme, “Diversity powers innovation,” underscores the cross-cutting nature of Children’s research that aims to transform pediatric care.

Ricardo Munoz

Ricardo Muñoz, M.D., joins Children’s National as Chief of Cardiac Critical Care Medicine, Executive Director of Telemedicine and Co-Director of Heart Institute

Ricardo Munoz

Children’s National Health System is pleased to announce Ricardo Muñoz, M.D., as chief of the Division of Cardiac Critical Care Medicine and co-director of the Children’s National Heart Institute. Dr. Muñoz also will serve as the executive director of Telemedicine Services at Children’s National, working to leverage advances in technology to improve access to health care for underserved communities and developing nations.

Within the new division of Cardiac Critical Care Medicine, Dr. Muñoz will oversee the work of a multidisciplinary team, including critical care nurse practitioners and nurses, respiratory and physical therapists, nutritionists, social workers and pharmacists, in addition to a medical staff with one of the highest rates of double-boarded specialists in cardiology and critical care.

“We are honored to welcome Dr. Ricardo Muñoz to Children’s National,” says David Wessel, M.D., executive vice president and chief medical officer of Hospital and Specialty Services. “He is a pioneer and innovator in the fields of cardiac critical care and telemedicine and will undoubtedly provide a huge benefit to our patients and their families along with our cardiac critical care and telemedicine teams.”

Dr. Muñoz comes to Children’s National from Children’s Hospital of Pittsburgh of UPMC. During his 15-year tenure there, he established the cardiac intensive care unit and co-led the Heart Center in a multidisciplinary effort to achieve some of the best outcomes in the nation. He also is credited with pioneering telemedicine for pediatric critical care, providing nearly 4,000 consultations globally.

“Children’s National has a longstanding reputation of excellence in cardiac critical care, and I am pleased to be able to join the team in our nation’s capital to not only deliver top-quality care to patients regionally, but also around the world,” says Dr. Muñoz. “The early identification and treatment of pediatric congenital heart disease patients has made rapid improvements in recent decades, but there is a shortage of intensivists to care for these children during what is often a complex recovery course.”

Dr. Muñoz attended medical school at the Universidad del Norte, Barranquilla, Colombia, and completed his residency in pediatrics at the Hospital Militar Central, Bógota, Colombia. He continued his training as a general pediatrics and pediatric critical care fellow at Massachusetts General Hospital, and as a pediatric cardiology fellow at Boston Children’s Hospital. He then joined the faculty at Harvard Medical School and served as an attending physician in the Cardiac Intensive Care Unit at Boston Children’s.

Dr. Muñoz is board certified in pediatrics, pediatric critical care and in pediatric cardiology. He is a fellow of the American Academy of Pediatrics, the American College of Critical Care Medicine and the American College of Cardiology. Additionally, he is the primary editor and co-author of multiple textbooks and award-winning handbooks in pediatric cardiac intensive care, including Spanish language editions.

Murfad Peer

Mechanically-assisted circulation for the failing Fontan

Murfad Peer

“Right now, the only way to really fix a failing Fontan is with a heart transplant, but the number of donor hearts is fixed and the number of people needing transplants has been increasing over time,” explains Murfad Peer, M.D. “So we are in a really tight spot. We need to do something, and we need to do it quickly.”

The only treatment currently available for patients born with single ventricle heart defects is the Fontan operation. And, while the operation provides excellent long-term palliation and survival, Fontan hearts eventually fail, and there are limited treatment options to help these patients make it to a heart transplant. A team led by  Murfad Peer, M.D., a cardiac surgeon at Children’s National, is trying to increase the survivorship of these patients with a heart pump.

“Right now, the only way to really fix a failing Fontan is with a heart transplant, but the number of donor hearts is fixed and the number of people needing transplants has been increasing over time,” explains Dr. Peer. “Most of these Fontan patients are so sick they are not even candidates for a transplant. So we are in a really tight spot. We need to do something, and we need to do it quickly.”

Currently in the United States, more than 800 Fontan procedures are done every year. The operation involves connecting the superior and inferior vena cava directly to the pulmonary artery so that deoxygenated blood flows straight to the lungs.

“When you do a Fontan, you do a series of surgeries that basically bypass the right heart, so that blood flow to the lungs is passive — it’s going to the lungs because of venous pressure,” says Dr. Peer. “There’s no ventricle actually pumping blood directly to the lungs.”

So, while the Fontan operation has facilitated the survival of a generation of children born with congenital heart disease, it does not recreate normal circulation. And, after about 15 to 20 years, the pressure on the right side of the heart becomes so high in some patients that blood starts backing up into the veins, resulting in organ failure.

One way to keep blood flowing is by adding a pump. Dr. Peer and his team hypothesized this could be accomplished by returning circulation to the way it was before the Fontan operation, and then supporting the ventricle with a standard commercially available continuous flow ventricular assist device (VAD) that pumps blood into the lungs and the aorta.

“We took a commercially available left-ventricle assist device and split the outflow graft so that it could flow both into the systemic circulation and into the lungs,” says Dr. Peer.

The team tested their mechanically assisted single ventricle circulation (MASVC) in an animal model of functionally univentricular circulation, and they were able to sustain the animal for two hours. The results were published in January 2018, in the World Journal for Pediatric and Congenital Heart Surgery.

Going forward, the team plans on testing MASVC for longer periods of time to determine its long-term durability. Dr. Peer is also working on computer modeling MASVC in a patient using an MRI.

NPosnack-Heart-image

NIH funding to improve devices and safeguard cardiovascular health

Nearly 15 million blood transfusions are performed each year in the U.S., and pediatric patients alone receive roughly 425,000 transfused units. Endocrine-disrupting chemicals, such as bisphenol A and di-2-ethylhexyl-phthalate (DEHP), can leach from some plastic devices used in such transfusions. However, it remains unclear how many complications following a transfusion can be attributed to the interplay between local and systemic reactions to these chemical contaminants.

NPosnack-Heart-image

Top: Live, excised heart that is being perfused with a crystalloid buffer via the aorta. The heart is stained with a voltage-sensitive fluorescent dye, which is excited by an LED light source. Bottom, right: Cardiac action potentials are optically mapped across the epicardial surface in real-time by monitoring changes in the fluorescence signal that are proportional to changes in transmembrane voltage. Bottom, left: An activation map (middle) depicts the speed of electrical conduction across the heart surface. Credit: Rafael Jaimes, Ph.D.; Luther Swift, Ph.D.; Manelle Ramadan, B.S.; Bryan Siegel, M.D.; James Hiebert, B.S., all of Children’s National Health System; and Daniel McInerney, student at The George Washington University.

The National Heart, Lung and Blood Institute within the National Institutes of Health has awarded a $3.4 million, five-year grant to Nikki Gillum Posnack, Ph.D., assistant professor at the Children’s National Heart Institute within the Sheikh Zayed Institute for Pediatric Surgical Innovation (SZI) at Children’s National Health System, to answer that question and to provide insights that could accelerate development of safer biomaterials.

According to the Food and Drug Administration, patients who are undergoing IV therapy, blood transfusion, cardiopulmonary bypass or extracorporeal membrane oxygenation or who receive nutrition through feeding support tubes have the potential to be exposed to DEHP.

Posnack led a recent study that found that an experimental model exposed to DEHP experienced altered autonomic regulation, heart rate variability and cardiovascular reactivity and reported the findings Nov. 6, 2017, in the American Journal of Physiology. The pre-clinical model study is the first to show such an association between phthalate chemicals used in everyday medical devices like IV tubing and cardiovascular health.

In the follow-on research, Posnack and colleagues will:

  • Use in vivo and whole heart models to define the extent to which biomaterial leaching and chemical exposure alters cardiovascular and autonomic function in experimental models
  • Determine whether biocompatibility and incidental chemical exposure are linked to cardiovascular and autonomic abnormalities experienced by pediatric patients post transfusion
  • Compare and contrast alternative biomaterials, chemicals and manufacturing techniques to identify safer transfusion device options.

“Ultimately, we hope to strengthen the evidence base used to inform decisions by the scientific, medical and regulatory communities about whether chemical additives that have endocrine-disrupting properties should be used to manufacture medical devices,” Posnack says. “Our findings also will highlight incentives that could accelerate development of alternative biomaterials, additives and fabrication techniques to improve safety for patients undergoing transfusion.”

Nikki Gillum Posnack

Experimental model study links phthalates and cardiovascular health

Nikki Gillum Posnack

“Because phthalate chemicals are known to migrate out of plastic products, our study highlights the importance of adopting safer materials, chemical additives and/or surface coatings for use in medical devices to reduce the risk of inadvertent exposure,” explains study senior author Nikki Gillum Posnack, Ph.D.

An experimental model exposed to di-2-ethylhexyl-phthalate (DEHP), a chemical that can leach from plastic-based medical devices, experienced altered autonomic regulation, heart rate variability and cardiovascular reactivity, according to a study published online Nov. 6, 2017 by the American Journal of Physiology. The pre-clinical model study is the first to show such an association between phthalate chemicals used in everyday medical devices like IV tubing and cardiovascular health.

“Plastics have revolutionized medical devices, transformed how we treat blood-based diseases and helped to make innovative cardiology procedures possible,” says Nikki Gillum Posnack, Ph.D., study senior author and assistant professor at the Children’s National Heart Institute within the Sheikh Zayed Institute for Pediatric Surgical Innovation (SZI) at Children’s National Health System. “Because phthalate chemicals are known to migrate out of plastic products, our study highlights the importance of adopting safer materials, chemical additives and/or surface coatings for use in medical devices to reduce the risk of inadvertent exposure.”

According to the Food and Drug Administration, patients who are undergoing IV therapy, blood transfusion, cardiopulmonary bypass or extracorporeal membrane oxygenation or who receive nutrition through feeding support tubes have the potential to be exposed to DEHP.

Patients undergoing extensive interventions to save their lives may be exposed to multiple plastic-based devices that supply oxygen and nutrition or that pump newly oxygenated blood to oxygen-starved organs.

“These interventions keep very fragile kids alive. What’s most important is getting patients the care they need when they need it,” Posnack says. “In the biomaterials field, our ultimate goal is to reduce inadvertent risks to patients that can result from contact with plastic products by identifying replacement materials or safer coatings to lower overall risk.”

In order to assess the safety of phthalate chemicals used in such medical devices, the Children’s-led research team implanted adult experimental models with radiofrequency transmitters that monitored their heart rate variability, blood pressure and autonomic regulation. Then, they exposed the experimental models to DEHP, a softener used in making the plastic polymer, polyvinyl chloride, flexible.

DEHP-treated pre-clinical models had decreased heart rate variability with lower-than-normal variation in the intervals between heart beats. The experimental models also showed an exaggerated mean arterial pressure response to ganglionic blockade. And in response to a stressor, the experimental models in the treatment group displayed enhanced cardiovascular reactivity as well as prolonged blood pressure recovery, according to the study team.

“The autonomic nervous system is a part of the nervous system that automatically regulates such essential functions as blood pressure and breathing rate without any conscious effort by the individual,” Posnack adds. “Because alterations in the autonomic balance provide an early warning sign of trouble – before symptoms of hypertension or atherosclerosis manifest – our findings underscore the importance of additional studies to explore the potential impact of phthalate chemicals on organ function.”

Billie Lou Short, M.D., chief of Children’s Division of Neonatology, called the paper an “important study” that builds on a foundation laid in the late 199os by Children’s researchers who were the first to show that plasticizers migrated from tubing in the extracorporeal membrane oxygenation (ECMO) circuit. Children’s researchers also led a study published in 2004 that evaluated the effect of plasticizers on the human reproductive system. A small number of adolescents who had undergone ECMO as newborns did not experience the complications that had been seen in in experimental models, Dr. Short says.

Posnack’s study co-authors include Rafael Jaimes III, Ph.D., SZI staff scientist; Meredith Sherman, SZI research technician; and Adam Swiercz, Narine Muselimyan and Paul J. Marvar, all of The George Washington University.

Nobuyuki Ishibashi

Children’s receives NIH grant to study use of stem cells in healing CHD brain damage

Nobuyuki Ishibashi

“Bone marrow stem cells are used widely for stroke patients, for heart attack patients and for those with developmental diseases,” explains Nobuyuki Ishibashi, M.D. “But they’ve never been used to treat the brains of infants with congenital heart disease. That’s why we are trying to understand how well this system might work for our patient population.”

The National Institutes of Health (NIH) awarded researchers at Children’s National Health System $2.6 million to expand their studies into whether human stem cells could someday treat and even reverse neurological damage in infants born with congenital heart disease (CHD).

Researchers estimate that 1.3 million infants are born each year with CHD, making it the most common major birth defect. Over the past 30 years, advances in medical technology and surgical practices have dramatically decreased the percentage of infants who die from CHD – from a staggering rate of nearly 100 percent just a few decades ago to the current mortality rate of less than 10 percent.

The increased survival rate comes with new challenges: Children with complex CHD are increasingly diagnosed with significant neurodevelopmental delay or impairment. Clinical studies demonstrate that CHD can reduce oxygen delivery to the brain, a condition known as hypoxia, which can severely impair brain development in fetuses and newborns whose brains are developing rapidly.

Nobuyuki Ishibashi, M.D., the study’s lead investigator with the Center for Neuroscience Research and director of the Cardiac Surgery Research Laboratory at Children’s National, proposes transfusing human stem cells in experimental models through the cardio-pulmonary bypass machine used during cardiac surgery.

“These cells can then identify the injury sites,” says Dr. Ishibashi. “Once these cells arrive at the injury site, they communicate with endogenous tissues, taking on the abilities of the damaged neurons or glia cells they are replacing.”

“Bone marrow stem cells are used widely for stroke patients, for heart attack patients and for those with developmental diseases,” adds Dr. Ishibashi. “But they’ve never been used to treat the brains of infants with congenital heart disease. That’s why we are trying to understand how well this system might work for our patient population.”

Dr. Ishibashi says the research team will focus on three areas during their four-year study – whether the stem cells:

  • Reduce neurological inflammation,
  • Reverse or halt injury to the brain’s white matter and
  • Help promote neurogenesis in the subventricular zone, the largest niche in the brain for creating the neural stem/progenitor cells leading to cortical growth in the developing brain.

At the conclusion of the research study, Dr. Ishibashi says the hope is to develop robust data so that someday an effective treatment will be available and lasting neurological damage in infants with congenital heart disease will become a thing of the past.

Dr. Laura Olivieri holding a 3D printed heart

Cardiology and radiology experts to participate in CMR 2018

Later this month, the international cardiovascular magnetic resonance (CMR) community will gather in Barcelona, Spain, for CMR 2018, a joint meeting organized by the European Association of Cardiovascular Imaging (EACVI) and the Society for Cardiovascular Magnetic Resonance (SCMR). Among the many attendees will be several cardiology and radiology experts from Children’s National Heart Institute:

  • Pediatric cardiology fellow Ashish Doshi, M.D., will be giving a talk titled, “Subendocardial resting perfusion defect in a case of acute fulminant myocarditis,” and will also present a poster titled, “Native T1 measurements in pediatric heart transplant patients correlate with history of prior rejection episodes.”
  • Pediatric cardiology fellow Rohan Kumthekar, M.D., will present a poster titled, “Native T1 values can identify pediatric patients with myocarditis.”
  • Cardiologist Laura Olivieri, M.D., will present two posters: “Native T1 measurements from CMR identify severity of myocardial disease over time in patients with Duchenne muscular dystrophy on therapy,” and “Feasibility of noncontrast T1 and T2 parametric mapping in assessment of acute ventricular ablation lesions in children.”
  • Pediatric cardiology fellow Neeta Sethi, M.D., will present a poster titled, “Cardiac magnetic resonance T2 mapping in the surveillance of acute allograft rejection in pediatric cardiac transplant patients.”

Additionally, Drs. Doshi and Sethi and Ileen Cronin, FNP-BC, a nurse practitioner in the Cardiac Catheterization Laboratory/Interventional Cardiac Magnetic Resonance (ICMR) Program, received travel awards to attend the conference.

CMR 2018 will be held January 31-February 3, 2018 and will focus on the theme of “Improving Clinical Value by Technical Advances.” The meeting’s emphasis will be on the common goal of improving clinical outcomes in cardiovascular disease through innovation in basic MR development and medical engineering.

Gram-positive-bacteria-Streptococcus-pyogenes

Assessing the risk factors in rheumatic heart disease

Gram-positive-bacteria-Streptococcus-pyogenes

Rheumatic heart disease is caused by untreated throat infections from the streptococcal bacterium. The infections progress into acute rheumatic fever and eventually weaken the valves of the heart.

Rheumatic heart disease (RHD) is the most commonly acquired cardiovascular disease in children and young adults. The devastating condition, which was endemic in the United States before 1950, is now relatively rare in the developed world due to social and economic development and the introduction of penicillin. But, in the developing world RHD remains nearly as common as HIV.

Fortunately, RHD is a cumulative disease and opportunities exist for early intervention. To further explore the utility of early diagnosis and intervention, a research team headed by Children’s National Heart Institute cardiologist Andrea Beaton, M.D., conducted a prospective natural history study of children with latent RHD.

RHD is caused by untreated streptococcal throat infections that progress into acute rheumatic fever (ARF) and eventually weaken the valves of the heart. While initial episodes of ARF occur almost exclusively during childhood, RHD most commonly presents in adolescents and young adults. This latent period between ARF and clinically apparent RHD is an ideal opportunity for early intervention, and screening echocardiography (echo) has emerged as a potentially powerful tool for early detection of RHD.

In their study published in the journal Circulation in September 2017, Dr. Beaton and her colleagues examined echocardiograms from children with latent RHD who were enrolled in the Ugandan National RHD registry. The researchers also developed models to search for risk factors and compare progression-free survival between patients who did and did not receive penicillin.

The team reports that children with moderate-to-severe latent RHD discovered by echo screening have poor outcomes. Children with both borderline and mild definite RHD have better outcomes but remain at substantial risk of progression. The researchers also found that children who are diagnosed at a younger age, and the presence of morphological mitral valve features, generally lead to unfavorable outcomes.

The authors conclude that children with moderate to severe RHD at screening should be considered for treatment as clinically diagnosed RHD, and that children with borderline or mild definite RHD at screening should, at a minimum, be maintained in close clinical follow up.

“It is clear that children found to have the earliest forms of RHD, seen only by echo, are at substantial risk for progression of disease. This study urges us forward to see if we can intervene to stop this progression once children are identified,” says Dr. Beaton.  “We are excited that our next project will be to do just that – a randomized clinical trial in Uganda to determine if penicillin can protect the hearts of children found to have latent RHD.”

effects of cardiopulmonary bypass surgery on the white matter of piglets.

The effects of cardiopulmonary bypass on white matter development

cardiopulmonary bypass

Nobuyuki Ishibashi, M.D., and a team of researchers looked the effects of cardiopulmonary bypass surgery on the white matter of an animal model.

Mortality rates for infants born with congenital heart disease (CHD) have dramatically decreased over the past two decades, with more and more children reaching adulthood. However, many survivors are at risk for neurodevelopmental abnormalities  associated with cardiopulmonary bypass surgery (CPB), including long-term injuries to the brain’s white matter and neural connectivity impairments that can lead to neurological dysfunction.

“Clinical studies have found a connection between abnormal neurological outcomes and surgery, but we don’t know what’s happening at the cellular level,” explains Nobuyuki Ishibashi, M.D., Director of the Cardiac Surgery Research Laboratory at Children’s National. To help shed light on this matter, Ishibashi and a team of researchers looked at the effects of CPB on the white matter of an animal model.

The research team randomly assigned models to receive one of three CPB-induced insults: a sham surgery (control group); full-flow bypass for 60 minutes; and 25°C circulatory arrest for 60 minutes. The team then used fractional anisotropy — a technique that measures the directionality of axon mylenation — to determine white matter organization in the models’ brains. They also used immunohistology techniques to assess the integrity of white matter oligodendrocytes, astrocytes and microglia.

The results, published in the Journal of the American Heart Association, show that white matter experiences region-specific vulnerability to insults associated with CPB, with fibers within the frontal cortex appearing the most susceptible. The team also found that fractional anisotropy changes after CPB were insult dependent and that regions most resilient to CPB-induced fractional anisotropy reduction were those that maintained mature oligodendrocytes.

From these findings, Ishibashi and his co-authors conclude that reducing alterations of oligodendrocyte development in the frontal cortex can be both a metric and a goal to improve neurodevelopmental impairment in the congenital heart disease population. “Because we are seeing cellular damage in these regions, we can target them for future therapies,” explains Ishibashi.

The study also demonstrates the dynamic relationship between fractional anisotropy and cellular events after pediatric cardiac surgery, and indicates that the technique is a clinically relevant biomarker in white matter injury after cardiac surgery.

Children’s National leaders join with Governor Martin O'Malley

Landmark CDC report finds easy, painless test decreases infant cardiac deaths by 33 percent

Stakeholders meeting at American College of Cardiology’s Heart House

Stakeholders meeting at American College of Cardiology’s Heart House in February 2012 to discuss U.S. implementation and recommendation of pulse ox screening.

Congenital heart disease (CHD) is the most common birth defect, affecting approximately eight out of every 1,000 babies born in the United States. The most severe cases, critical congenital heart disease (CCHD), affect three in every 1,000 babies. Just a few years ago, many of these seemingly healthy infants were discharged from the hospital only to suffer severe complications, brain damage or even death due to their undiagnosed conditions.

In 2009, Children’s National Cardiologist and Medical Director of Global Services Gerard Martin, M.D., and the nursing staff within the Children’s National Heart Institute took on this challenge with peers around the country by urging legislators and educating clinicians that implementing a simple, painless test called pulse oximetry (ox) could identify infants who may suffer from undetected CCHD.

Today, 49 out of 50 states in the United States mandate pulse ox screening, which uses a small, red light, or “probe,” to measure the percent oxygen saturation of hemoglobin in the arterial blood. Use of pulse ox also is included in the Recommended Uniform Screening Panel (RUSP), endorsed by the Secretary of the U.S. Department of Health and Human Services.

This week, the Centers for Disease Control and Prevention released a report presenting definitive evidence that these efforts are saving lives. Published in JAMA, the report shows a 33 percent reduction in pediatric CCHD deaths from 2007 to 2013 in states with mandated pulse ox screening compared to states without screening policies. The study also found a 21 percent drop in infant deaths from other or unspecified cardiac causes in those states. Applying the data to the United States as a whole, this equates to preventing the deaths of 120 newborns each year.

“This is a landmark moment for the countless parents, clinicians, industry partners, legislators and many others who fought tirelessly to have this lifesaving screening added to the routine panel of tests every child receives before they leave the hospital,” says Dr. Martin. “We now have concrete, measurable evidence that their efforts are saving lives.”

Physicians and staff at Children’s National and Holy Cross Hospital in Silver Spring, Md., began their campaign by initiating a research study to examine the feasibility of implementing pulse ox screening for CCHD in a community hospital setting. Their findings not only showed it was possible, but it also only required approximately 3.5 minutes per baby, and it could be integrated into existing workflow without adding additional nursing staff.

Children’s National leaders join with Governor Martin O'Malley

Children’s National leaders join with Governor Martin O’Malley and Maryland legislators for the signing of SB 786 and HB 714, mandating pulse oximetry screening across the state on May 19, 2011.

The findings also led to the development of an educational toolkit – now available in English, Spanish, Arabic, French, Chinese and Russian – which Dr. Martin and the Children’s National Heart Institute’s nursing staff have used to teach upwards of 3,000 hospitals, globally, how to implement the screening. Children’s National, in partnership with Baby’s First Test, also released two videos for parents and clinicians respectively, to forward knowledge about pulse ox.

Simultaneously, the Children’s National team worked as national and local advocacy leaders. Dr. Martin served as part of the federal Advisory Committee on Heritable Disorders in Newborns and Children that issued national recommendations to add screening for congenital heart disease to RUSP in 2011. The team also spearheaded efforts that led to the passage of legislative mandates and helped to implement screening for all newborns in Maryland, Virginia and Washington, D.C.

“When we started this work nearly a decade ago, I’d meet so many moms who were crying because they had lost their child to critical congenital heart disease. Now, we meet moms who are crying because their baby’s condition has been found and their life has been saved,” says Dr. Martin. “This report shines a light on so many heroes–the parents who spoke up, the members of the federal advisory committee, the nurses and clinicians who learned and taught others how to implement the screening. Today is a victory for all of us.”

Dr. Martin hopes this announcement will prompt Idaho, the only state that has not adopted universal CCHD screening, to take action. He also says health leaders need to continue to invest in smarter technology and testing capabilities, as well as advance training and education for more thorough prenatal ultrasounds, so that every baby with CCHD is found early and receives lifesaving care.

Zhe Han

Research led by Zhe Han featured on cover of JASN, leading kidney disease journal

Journal of the American Society of Nephrology September 2017 cover

Coenzyme Q10, one of the best-selling nutrient supplements to support heart health also could be beneficial for kidney health, according to research conducted in transgenic fruit flies that was led by Zhe Han, Ph.D., associate professor at Children’s Center for Cancer and Immunology Research.

Nephrocytes, filtration kidney cells in Drosophila, require the Coq2 gene for protein reabsorption, toxin sequestration and critical cell ultrastructure.  Silencing the Coq2 gene results in aberrantly localized nephrocyte slit diaphragms and deformed lacunar channels, Han and co-authors found. Nephrocytes closely resemble the podocytes of the human kidney.

The research team’s paper, published online April 2017, this fall was featured on the cover of Journal of the American Society of Nephrology, the No. 1 kidney disease journal.

“I am honored that the JASN editors chose to feature my lab’s work on the cover of this prestigious journal,” Han says. “This underscores the utility of our gene-replacement approach, which silenced the fly homolog in the tissue of interest – here, the kidney cells – and provided a human gene to supply the silenced function.”

StethAid is a low-cost mobile device-based digital stethoscope that lets pediatric healthcare providers know instantly if a heart murmur is innocent or a signal of a more pathological heart problem

AusculTech DX wins Washington Business Journal 2017 Innovation Award

StethAid is a low-cost mobile device-based digital stethoscope that lets pediatric healthcare providers know instantly if a heart murmur is innocent or a signal of a more pathological heart problem

StethAid is a low-cost mobile device-based digital stethoscope that lets pediatric healthcare providers know instantly if a heart murmur is innocent or a signal of a more pathological heart problem.

AusculTech DX, a start-up company that formed within the Sheikh Zayed Institute for Pediatric Surgical Innovation at Children’s National Health System, was selected as a Washington Business Journal 2017 Innovation Award honoree for their device, StethAid.

StethAid is a low-cost mobile device-based digital stethoscope that lets pediatric healthcare providers know instantly if a heart murmur is innocent or a signal of a more pathological heart problem. The device was developed by Robin Doroshow, M.D., a pediatric cardiologist at Children’s National, and Raj Shekhar, Ph.D., a principal investigator with the Sheikh Zayed Institute for Pediatric Surgical Innovation at Children’s National to help eliminate unnecessary referrals of patients with Still’s murmurs to pediatric cardiologists.

In studying her extensive library of recorded heartbeats, Dr. Doroshow noticed that the Still’s murmur had the same distinct musical tone, regardless of the patient’s age, size and heart rate. When she realized that there was likely a way to teach a computer to recognize the tone, she approached Shekhar with her idea. He developed a highly accurate computer algorithm, based on AI (artificial intelligence) principles, to recognize the consistent Still’s tone and worked to develop the digital device. In early 2015, the team formed AusculTech DX. In early 2016, a clinical prototype was developed and they began testing the device.

The Washington Business Journal’s annual Innovation Awards honor Greater Washington companies, agencies and teams working to keep the metro on the cutting edge in tech, health care, cybersecurity and more. AusculTech DX was one of the 15 honorees selected for the 2017 Innovation Awards.

Catherine Limperopoulous

Brain impairment in newborns with CHD prior to surgery

Catherine Limperopoulous

Children’s National researchers led by Catherine Limperopoulos, Ph.D., demonstrate for the first time that the brains of high-risk infants show signs of functional impairment before they undergo corrective cardiac surgery.

Newborns with congenital heart disease (CHD) requiring open-heart surgery face a higher risk for neurodevelopmental disabilities, yet prior studies had not examined whether functional brain connectivity is altered in these infants before surgery.

Findings from a Children’s National Health System study of this question suggest the presence of brain dysfunction early in the lives of infants with CHD that may be associated with neurodevelopmental impairments years later.

Using a novel imaging technique, Children’s National researchers demonstrated for the first time that the brains of these high-risk infants already show signs of functional impairment even before they undergo corrective open heart surgery. Looking at the newborns’ entire brain topography, the team found intact global organization – efficient and effective small world networks – yet reduced functional connectivity between key brain regions.

“A robust neural network is critical for neurons to travel to their intended destinations and for the body to carry out nerve cells’ instructions. In this study, we found the density of connections among rich club nodes was diminished, and there was reduced connectivity between critical brain hubs,” says Catherine Limperopoulos, Ph.D., director of the Developing Brain Research Laboratory at Children’s National and senior author of the study published online Sept. 28, 2017 in NeuroImage: Clinical. “CHD disrupts how oxygenated blood flows throughout the body, including to the brain. Despite disturbed hemodynamics, infants with CHD still are able to efficiently transfer neural information among neighboring areas of the brain and across distant regions.”

The research team led by Josepheen De Asis-Cruz, M.D., Ph.D., compared whole brain functional connectivity in 82 healthy, full-term newborns and 30 newborns with CHD prior to corrective heart surgery. Conventional imaging had detected no brain injuries in either group. The team used resting state functional connectivity magnetic resonance imaging (rs-fcMRI), a imaging technique that characterizes fluctuating blood oxygen level dependent signals from different regions of the brain, to map the effect of CHD on newborns’ developing brains.

The newborns with CHD had lower birth weights and lower APGAR scores (a gauge of how well brand-new babies fare outside the womb) at one and five minutes after birth. Before the scan, the infants were fed, wrapped snugly in warm blankets, securely positioned using vacuum pillows, and their ears were protected with ear plugs and ear muffs.

While the infants with CHD had intact global network topology, a close examination of specific brain regions revealed functional disturbances in a subnetwork of nodes in newborns with cardiac disease. The subcortical regions were involved in most of those affected connections. The team also found weaker functional connectivity between right and left thalamus (the region that processes and transmits sensory information) and between the right thalamus and the left supplementary motor area (the section of the cerebral cortex that helps to control movement). The regions with reduced functional connectivity depicted by rs-fcMRI match up with regional brain anomalies described in imaging studies powered by conventional MRI and diffusion tensor imaging.

“Global network organization is preserved, despite CHD, and small world brain networks in newborns show a remarkable ability to withstand brain injury early in life,” Limperopoulos adds. “These intact, efficient small world networks bode well for targeting early therapy and rehabilitative interventions to lower the newborns’ risk of developing long-term neurological deficits that can contribute to problems with executive function, motor function, learning and social behavior.”