Cardiology and Heart Surgery

illustration of brain with stem cells

Innovative phase 1 trial to protect brains of infants with CHD during and after surgery

A novel phase 1 trial looking at how best to optimize brain development of babies with congenital heart disease (CHD) is currently underway at Children’s National Hospital.

Children with CHD sometimes demonstrate delay in the development of cognitive and motor skills. This can be a result of multiple factors including altered prenatal oxygen delivery, brain blood flow and genetic factors associated with surgery including exposure to cardiopulmonary bypass, also known as the heart lung machine.

This phase 1 trial is the first to deliver mesenchymal stromal cells from bone marrow manufactured in a lab (BM-MSC) into infants already undergoing cardiac surgery via cardiopulmonary bypass. The hypothesis is that by directly infusing the MSCs into the blood flow to the brain, more MSCs quickly and efficiently reach the subventricular zone and other areas of the brain that are prone to inflammation. The trial is open to eligible patients ages newborn to six months of age.


Learn more in this overview video.

The trial is part of a $2.5 million, three-year grant from the National Institutes of Health (NIH) led by Richard Jonas, M.D.Catherine Bollard, M.B.Ch.B., M.D., and Nobuyuki Ishibashi, M.D.. The project involves collaboration between the Prenatal Cardiology program of Children’s National Heart Institute, the Center for Cancer and Immunology Research, the Center for Neuroscience Research and the Sheikh Zayed Institute for Pediatric Surgical Innovation.

“NIH supported studies in our laboratory have shown that MSC therapy may be extremely helpful in improving brain development in animal models after cardiac surgery,” says Dr. Ishibashi. “MSC infusion can help reduce inflammation including prolonged microglia activation that can occur during surgery that involves the heart lung machine.”

Staff from the Cellular Therapy Laboratory, led by director Patrick Hanley, Ph.D., manufactured the BM-MSC at the Center for Cancer and Immunology Research, led by Dr. Bollard.

The phase 1 safety study will set the stage for a phase 2 effectiveness trial of this highly innovative MSC treatment aimed at reducing brain damage, minimizing neurodevelopmental disabilities and improving the postoperative course in children with CHD. The resulting improvement in developmental outcome and lessened behavioral impairment will be of enormous benefit to individuals with CHD.

For more information about this new treatment, contact the clinical research team: Gil Wernovsky, M.D., Shriprasad Deshpande, M.D., Maria Fortiz.

Asha Moudgil examines patient

Social determinants of cardiovascular health in African American children with CKD

Asha Moudgil examines patient

In a recent study, Asha Moudgil, M.D., and colleagues looked at differences in socioeconomic factors and subclinical cardiovascular disease markers by race in chronic kidney disease patients.

Children with chronic kidney disease (CKD) are known to have an increased risk for cardiovascular (CV) disease. African American children with CKD are also disproportionately affected by socioeconomic disadvantages related to systemic racism.

In a recent analysis of 3,103 visits from 628 children enrolled in the Chronic Kidney Disease in Children (CKiD) study, Children’s National Hospital researchers Kristen Sgambat, Ph.D., and Asha Moudgil, M.D., and their colleagues found that African American children with CKD had increased left ventricular mass index, more ambulatory hypertension and differences in lipid profile compared with Caucasian children. After adjusting for socioeconomic factors (public health insurance, household income, maternal education, food insecurity, abnormal birth history), a trend towards attenuation of the differences in these CV markers was observed.

The authors of the study conclude that, “as many social determinants of health were not captured by our study, future research should examine effects of systemic racism on CV health in this population.”

Read the full study in the American Journal of Kidney Diseases.

close up of an IV bag

Carnitine may improve heart function in children receiving CRRT

close up of an IV bag

A first-of-its-kind study demonstrated that IV carnitine supplementation is associated with improvement in myocardial strain and repletion of plasma total and free carnitine in children with AKI receiving CRRT.

Supplementation of a special nutrient could help improve heart function in children receiving continuous dialysis in critical care units. The nutrient carnitine plays an essential role in producing energy for use by heart and skeletal muscles. Critically ill children with acute kidney dysfunction often need a continuous dialysis therapy (also known as CRRT, continuous renal replacement therapy) to help remove toxins while kidneys are not working. An unintended consequence of this CRRT is removal of carnitine. Often these critically ill children are unable to eat by mouth and therefore can’t receive carnitine unless it is supplemented. Children’s National Hospital researchers have proven that intravenous carnitine supplementation is associated with repletion of the body’s carnitine supply and may cause improvement in heart function as shown by heart strain analysis (which detects subclinical cardiac dysfunction that may not be apparent by traditional echocardiography).

In a first-of-its-kind study, the Children’s National researchers, Asha Moudgil, M.D., Kristen Sgambat, M.D., and Sarah Clauss, M.D., investigated carnitine deficiency in children receiving CRRT. They demonstrated for the first time that these children become severely deficient in carnitine after being on CRRT for >1 week, and that carnitine supplementation is associated with carnitine repletion and improved heart function. This knowledge can help to guide clinical care, as carnitine can be easily added to the IV nutritional formulations that are typically given to these patients.

Although little was previously known about carnitine status in patients with acute kidney injury (AKI) receiving CRRT, iatrogenic carnitine deficiency related to chronic hemodialysis (HD) in patients with end stage renal disease is a well-known phenomenon. It was theorized that given the continuous removal of solutes by CRRT in combination with lack of dietary intake and impaired production of endogenous carnitine by the kidney in critically ill children with AKI, carnitine would be rapidly depleted.

The latest controlled pilot study (NCT01941823) of 48 children hypothesized that carnitine supplementation would improve left ventricular function in children receiving CRRT. Children ages 1-21 years with AKI requiring CRRT, who were admitted to the pediatric intensive care unit at Children’s National Hospital from 2015 to 2018 were eligible to prospectively enroll in the “CRRT Intervention group,” if they were total parenteral nutrition (TPN)-dependent and not receiving any enteral or IV carnitine prior to enrollment.

The researchers say that “An exciting collaborative effort between nephrology and cardiology made it possible to use a sophisticated technology known as speckle tracking imaging to study the effects of carnitine on heart in this population.” This technology can identify early changes in heart motion, also known as cardiac strain that may not be detected using standard heart imaging techniques.

This is the first study to demonstrate that IV carnitine supplementation is associated with improvement in myocardial strain and repletion of plasma total and free carnitine in children with AKI receiving CRRT. A cohort of pediatric chronic HD patients demonstrated similar benefits in a prior study conducted by Drs. Moudgil and Sgambat. Compared with chronic HD, carnitine is even more rapidly depleted by CRRT, with losses approximating 80% of intake. The effect of carnitine deficiency and supplementation on cardiovascular function in patients receiving CRRT had not been previously investigated.

The pilot study by Drs. Moudgil, Sgambat, and Clauss was single center and limited by small sample size. The small sample size may have limited the ability to detect significant differences in demographics and clinical characteristics and multivariable analyses could not be performed. However, given that it is a pilot study, the findings provide a solid launching point for future investigations to show how supplementation can be best utilized to optimize cardiac outcomes in children receiving CRRT.

Lee Beers

Lee Beers, M.D., F.A.A.P, begins term as AAP president

Lee Beers

“The past year has been a stark reminder about the importance of partnership and working together toward common goals,” says Dr. Beers. “I am humbled and honored to be taking on this role at such a pivotal moment for the future health and safety of not only children, but the community at large.”

Lee Savio Beers, M.D., F.A.A.P., medical director of Community Health and Advocacy at the Child Health Advocacy Institute (CHAI) at Children’s National Hospital, has begun her term as president of the American Academy of Pediatrics (AAP). The AAP is an organization of 67,000 pediatricians committed to the optimal physical, mental and social health and well-being for all children – from infancy to adulthood.

“The past year has been a stark reminder about the importance of partnership and working together toward common goals,” says Dr. Beers. “I am humbled and honored to be taking on this role at such a pivotal moment for the future health and safety of not only children, but the community at large.”

Dr. Beers has pledged to continue AAP’s advocacy and public policy efforts and to further enhance membership diversity and inclusion. Among her signature issues:

  • Partnering with patients, families, communities, mental health providers and pediatricians to co-design systems to bolster children’s resiliency and to alleviate growing pediatric mental health concerns.
  • Continuing to support pediatricians during the COVID-19 pandemic with a focus on education, pediatric practice support, vaccine delivery systems and physician wellness.
  • Implementation of the AAP’s Equity Agenda and Year 1 Equity Workplan.

Dr. Beers is looking forward to continuing her work bringing together the diverse voices of pediatricians, children and families as well as other organizations to support improving the health of all children.

“Dr. Beers has devoted her career to helping children,” says Kurt Newman, M.D., president and chief executive officer of Children’s National. “She has developed a national advocacy platform for children and will be of tremendous service to children within AAP national leadership.”

Read more about Dr. Beer’s career and appointment as president of the AAP.

stethoscope and stress ball in heart shape

First registry specifically for adult congenital heart disease launches

stethoscope and stress ball in heart shape

Although nearly 2 million adults in the United States are living with a congenital heart defect, it’s been historically difficult to gather data on these conditions and to identify patient needs. To address this challenge, Children’s National Hospital and the Heart Research Alliance, in partnership with the Adult Congenital Heart Association and University of California San Francisco, developed the Congenital Heart Initiative, a registry specifically for adult congenital heart disease (ACHD) patients.

The Congenital Heart Initiative aims to:

  • Understand how to improve the quality of life for adults with congenital heart defects
  • Improve our understanding of the ACHD population for patients, providers and researchers
  • Inform future research projects of needs within the ACHD community
  • Spur innovation within congenital heart disease treatment
  • Fundamentally change the way America understands and cares for ACHD patients

The registry will collect data from brief surveys sent to enrollees every six months, which will be used to gain a deeper understanding of the experiences of ACHD patients. By reshaping the way that ACHD is understood by both patients and clinicians, the registry can improve the lives and futures of adults living with congenital heart defects.

“Our long-term goal is to develop a platform for everyone in the community to come together and learn more about CHD,” says Anitha John, M.D., Ph.D., medical director of the Washington Adult Congenital Heart Program at Children’s National, who led development of this initiative. “We hope that this effort will be the start of a resource to allow patients and researchers to come together and learn more, together, about congenital heart disease.”

Children’s National Hospital is joined in this effort by six other U.S. organizations, including:

  • University of California San Francisco
  • Heart Research Alliance (formerly the Health eHeart Alliance)
  • Adult Congenital Heart Disease Cause Group
  • Eureka
  • Adult Congenital Heart Association (ACHA)
  • Alliance for Adult Research in Congenital Cardiology (AARCC)

Several other organizations serve as advisors to the initiative, including:

  • National Heart, Lung, and Blood Institute (NHLBI)
  • Centers for Disease Control and Prevention (CDC)
  • American College of Cardiology, Adult Congenital & Pediatric Cardiology (ACPC) Section
  • Cardiac Networks United

People with congenital heart disease who are 18 years of age or older may enroll in the registry and volunteer to participate in research conducted within the initiative. Learn more at: https://chi.eurekaplatform.org.

Dr. Craig Sable

AHA doubles down on global support, prevention and research in rheumatic heart disease

Dr. Craig Sable

Dr. Craig Sable and pediatric cardiology colleagues led the creation of a scientific statement and advocacy statement focused on eradicating RHD.

A pair of articles appearing in the American Heart Association’s (AHA) journal Circulation lays out a call to action for advocacy and scientific priorities crucial to the global eradication of rheumatic heart disease (RHD).

Cardiologists from Children’s National Hospital, and others who completed their pediatric cardiology fellowships at Children’s National before moving on to careers at other institutions, have been active proponents and advocates for these efforts for many years and led key research and clinical care efforts related to RHD in other countries of the world.

These cardiologists, including the associate chief of cardiology at Children’s National, Craig Sable, M.D., who previously served as chair of the AHA Council on Lifelong Congenital Heart Disease and Heart Health in the Young, also helped lead the creation of these new published statements.

Contemporary diagnosis and management of rheumatic heart disease: Implications for closing the gap

This clinical and research statement “seeks to examine the current state of-the-art recommendations and to identify gaps in diagnosis and treatment globally that can inform strategies for reducing disease burden.”

Key recommendations and related challenges were mapped out, including:

  • The need for echocardiography screening based on World Heart Federation echocardiographic criteria for identifying patients earlier, when prophylaxis is more likely to be effective. However, the authors note that several important questions need to be answered before this can translate into public policy.
  • The creation of population-based registries to effectively enable optimal care and secondary penicillin prophylaxis within available resources, though the team acknowledges that challenges with penicillin procurement and concern with adverse reactions in patients with advanced disease remain important issues.
  • Heart failure management, prevention, early diagnosis and treatment of endocarditis, oral anticoagulation for atrial fibrillation and prosthetic valves used as vital therapeutic adjuncts.
  • Multidisciplinary team management of health of women with unoperated and operated rheumatic heart disease before, during and after pregnancy is the best approach, though it is a significant challenge.
  • Percutaneous balloon mitral valvuloplasty should be considered for patients with isolated mitral stenosis.
  • Timely heart valve surgery, especially valve repair for rheumatic mitral regurgitation, can mitigate the progression to heart failure, disability and death. However, some of these procedures are not available to the vast majority of patients in endemic regions.

The recommendations made in the scientific statement form the foundation for the advocacy companion document.

The AHA’s call to action for reducing the global burden of rheumatic heart disease: a policy statement from the AHA

The advocacy statement outlines five key areas of support:

  1. Professional healthcare worker education and training.
  2. Technical support for the implementation of evidence-based strategies for rheumatic fever/RHD prevention.
  3. Access to essential medications and technologies.
  4. Research.
  5. Advocacy to increase global awareness, resources and capacity for RHD control.

The authors write, “In bolstering the efforts of the American Heart Association to combat RHD, we hope to inspire others to collaborate, communicate and contribute.”

Speaking of the two statements as a whole, the authors of the scientific statement conclude that, “Ultimately, the combination of expanded treatment options, research and advocacy built on existing knowledge and science provides the best opportunity to address the burden of rheumatic heart disease.”

Read more about Children’s National Heart Institute’s research, education and clinical care in rheumatic heart disease.

Craig Sable, M.D., Associate Chief of the Division of Cardiology and Director of Echocardiography at Children’s National Health System, is working with hundreds of doctors to create a scalable solution to reduce the global burden of rheumatic heart disease (RHD). Dr. Sable received a lifetime achievement award — the 2018 Cardiovascular Disease in the Young (CVDY) Meritorious Achievement Award — from the American Heart Association for his work in Uganda.

Mended Little Hearts’ Volunteer of the Year, Maryann Mayhood, and her son Joseph delivered the Hospital of the Year award to Dr. Donofrio in November 2020.

Mended Little Hearts names Children’s National Hospital as ‘Hospital of the Year’

Mended Little Hearts’ Volunteer of the Year, Maryann Mayhood, and her son Joseph delivered the Hospital of the Year award to Dr. Donofrio in November 2020.

Mended Little Hearts’ Volunteer of the Year, Maryann Mayhood, and her son Joseph delivered the Hospital of the Year award to Dr. Donofrio in November 2020.

Children’s National Hospital was named Hospital of the Year by Mended Little Hearts, one of the top organizations in the U.S. for patients with congenital heart disease and their families. Children’s National was selected as the Hospital of the Year across all divisions of the Mended Little Hearts national network and the Washington, D.C. region. The hospital is recognized with the award for its efforts to empower Mended Little Hearts volunteers and make it possible for the group to provide peer support and education to children and adults with congenital heart disease, their families and the surrounding communities.

“It’s an honor to be recognized as a champion by a group like Mended Little Hearts that truly represents the voices and needs of patients and their families. We embrace and encourage their work because we know that providing the best care for children and their families goes beyond simply outstanding clinical service,” says Charles Berul, M.D., chief of Cardiology and co-director of the Children’s National Heart Institute. “We are privileged to have a group of dedicated volunteers from Mended Little Hearts who are willing to work side-by-side with our team to share peer support, education and guidance for our families at Children’s National.”

Though many in-person activities are currently on hold or held virtually for the health and safety of everyone during the COVID-19 public health emergency, Children’s National and Mended Little Hearts continue to coordinate closely together to support families as much as possible by making virtual connections and via the Mended Little Hearts “Bravery Bags,” which are given to every family and include personal essentials for a hospital stay as well as important guidance such as questions to ask care providers and how to seek more information about the care plan.

For the last few years, the hospital has also provided space within the hospital for the group to host family breakfasts and other events, making sure families have access to the information and support items they need during a hospital stay. They are also welcomed to many of the hospital’s annual events for adults and children with congenital heart disease and their families, to connect and share experiences.

“We are honored to recognize Children’s National Hospital for the outstanding work they have done to support heart patients and their families,” said Mended Hearts Inc. President Ron Manriquez. “That they have won this award is proof of the deep commitment they have to their members, families and the community at large. We are grateful for the work they do to support the Mended Little Hearts mission.”

Mended Little Hearts and its parent group, Mended Hearts, are organizations that inspire hope and seek to improve the quality of life for heart patients and their families through ongoing peer-to-peer support.

pile of plastic bottles

The linkage between chemicals used in plastics and cardiovascular disease

pile of plastic bottles

For people across the globe, plastics are synonymous with modern life and it’s impossible to avoid exposure to them, including clinical environments where a variety of frequently used materials, such as tubing and blood storage bags, are made from plastics.

For people across the globe, plastics are synonymous with modern life and it’s impossible to avoid exposure to them, including clinical environments where a variety of frequently used materials, such as tubing and blood storage bags, are made from plastics. Led by Nikki Posnack, Ph.D, principal investigator at The Sheikh Zayed Institute for Pediatric Surgical Innovation at Children’s National Hospital, a team of Children’s National researchers has been studying the potential effects of chemicals found in plastics, such as BPA and DEHP, as possible contributors to cardiovascular disease.

Along with conducting proprietary studies of the potential effects, Posnack and her team recently reviewed available scientific studies to further identify and illuminate the potential links between exposure to the synthetic additives contained in plastics and cardiovascular mortality. The article was published this month in Nature Reviews Cardiology.

In the article Posnack cites a 10-year longitudinal study with the finding that high exposure to BPA was associated with a 46-49% higher hazard ratio for cardiovascular and all-cause mortality, compared with low exposure to BPA.

“Plastics may be indispensable materials, but their ubiquity does raise concerns about the effects of our continuous exposure to plasticizer additives like di(2-ethylhexyl) phthalate (DEHP) and synthetic chemicals used to create polymers like BPA,” said Posnack. “Although disease causation can be difficult to pinpoint in population and epidemiological studies, experimental work has clearly demonstrated a direct link to plastic chemicals and cardiac dysfunction. It is clear that future collaborative endeavors are necessary to bridge the gap between experimental, epidemiological and clinical investigations to resolve the impact of plastics on cardiovascular health.”

Nikki Gillum Posnack

Nikki Posnack, Ph.D, principal investigator at The Sheikh Zayed Institute for Pediatric Surgical Innovation at Children’s National Hospital.

Posnack added that, given the omnipresence of plastics and their related chemicals, biomonitoring studies have reported detectable levels of DEHP and BPA in 75-90% of the population. Occupational or clinical environments can also result in elevated exposures to these dangerous chemicals. Previous epidemiological studies have reported links between elevated urinary levels of phthalate or bisphenol, common additives in plastic, and an increased risk of coronary and peripheral artery disease, chronic inflammation, myocardial infarction, angina, suppressed heart rate variability and hypertension.

Additionally, available research has shown that incomplete polymerization or degradation of BPA-based plastic products can result in unsafe human exposure to BPA. Despite these links, the article points out, both BPA and DEHP are still manufactured in high volumes and are used to produce a wide variety of consumer and commercial products.

Further exploring implications for pediatrics, a June 2020 article published by Posnack in Birth Defects Research looks at the potential effects of plastic chemicals on the cardiovascular health of fetal, infant and pediatric groups. The article highlighted experimental work that suggests plasticizer chemicals such as bisphenols and phthalates may exert negative influence on pediatric cardiovascular health. The article systematically called out areas of concern supported by research findings. Also addressing current gaps in knowledge, Posnack outlined future research endeavors that would be needed to resolve the relationship between chemical exposures and the impact on pediatric cardiovascular physiology.

In related work, Posnack and her team are expanding their work on plastics used in blood bags to also investigate the role of blood storage duration on health outcomes. A recently published first study demonstrates that “older” blood products (stored 35 or more days) directly impact cardiac electrophysiology, using experimental models. Published October 22, 2020 in the Journal of the American Heart Association, the study concludes that the cardiac effects are likely caused by biochemical alterations in the supernatant from red blood cell units that occur over time, including but not limited to, hyperkalemia (elevated potassium levels).

a telehealth video visit with a patient family

Steady rates of patient satisfaction, reimbursement for cardiac telehealth during COVID-19

a telehealth video visit with a patient family

In the first two weeks of COVID-19’s major impact on the U.S., Children’s National Hospital moved most of its subspecialty in-person day-to-day clinics to virtual care. Children’s National Heart Institute was one of the first divisions to offer telehealth visits — in part because the team was an early adopter of telehealth in cardiology for both physician-to-physician consultations and direct-to-patient care, and stood poised to widely implement it.

A poster presentation at the American Heart Association Scientific Sessions 2020 quantified how the rapid transition to direct-to-consumer telehealth services impacted families with children who have congenital heart disease. The findings were presented by first author Kristine Mehrtens, M.S., B.S.N., R.N., C.P.N., clinical manager for the Heart Institute’s Ambulatory Services.

The team found that though in-person cardiology visits decreased during the COVID-19 pandemic, direct-to-patient telehealth visits were able to partially compensate for the sudden drop.

Additionally, payer reimbursement rates for these direct-to-consumer telehealth visits were similar to in-person clinic visits.

”This is exciting as prior to COVID-19  we have seen a lower reimbursement rates for these cardiology direct-to-consumer telehealth visits compared to in-person cardiology clinic visits,” said Ashraf S. Harahsheh, M.D., a pediatric cardiologist at Children’s National Hospital who has utilized direct-to-consumer telehealth visits since 2016 and is a senior author on the new study.

Patient satisfaction scores for care providers, including the likelihood of recommending a care provider from Children’s National Hospital, was the same for telehealth follow-up visits as it was for in-person clinic visits before the pandemic.

“As a multidisciplinary team, we agreed that diagnostic studies such as echocardiograms were important to include with follow-up visits,” says Mehrtens. “Together we developed a strategy to ensure we could meet the needs of the patients and also safely conduct in-person visits when necessary.”

Why is this important?

The pandemic and the resulting temporary halt to in-person, non-urgent/emergent visits earlier this year put the most vulnerable people with congenital heart disease at high risk for complications or worsening of their existing heart disease because they are unable to follow the recommended schedule for follow-ups.

The readiness of the Children’s Heart Institute team to quickly move to a telehealth platform successfully bridged the gap between in-person visits for some patients, allowing cardiology surveillance to continue safely.

“I am proud of our team of physicians and advanced care providers,” Harahsheh concludes. “We went from three providers (8%) pre-COVID 19 to 31 (79%) providers offering direct-to-consumer telehealth visits during the pandemic.”

What’s next?

Building on previous, smaller studies of telehealth before the pandemic began, the team will continue to conduct research to assess the safety and efficacy of these telehealth visits over time. The increase in patients who are continuing to see their providers for routine follow-ups via telehealth will allow a larger sample for effective study of this care model.

American Heart Association Scientific Sessions 2020
Impact of Telemedicine on Pediatric Cardiac Center’s Ambulatory Response to the 2019 Novel Coronavirus Disease (covid-19) Pandemic
P1692
9:00am – 10:00am
Fri, Nov 13  (CST)

Read additional news stories about cardiology telehealth:

newborn in ICU

Cardiac technology advances show promise for kids but only if right-sized

newborn in ICU

“Smaller patients, and those with congenital heart disease, can benefit from minimally-invasive methods of delivering pacemakers and defibrillators without the need for open-chest surgery,” says Charles Berul, M.D.

How to address the growing need for child-sized pacemakers and defibrillators, and finding better surgical techniques to place them, is the topic of an invited session called The Future is Now (or Coming Soon): Updates on New Technologies in Congenital Heart Care at the 2020 American Heart Association Scientific Sessions.

“Smaller patients, and those with congenital heart disease, can benefit from minimally-invasive methods of delivering pacemakers and defibrillators without the need for open-chest surgery,” says Charles Berul, M.D., co-director of the Children’s National Heart Institute and chief of Cardiology at Children’s National Hospital, who presented at the session.

“This unmet need can only be met by innovative pediatric research, geared towards miniaturization technologies for use in the smallest of children,” he says.

His presentation focused on the devices and approaches that have caught the attention of pediatric cardiology, such as pacemakers and subcutaneous defibrillators designed without lead wires, as well as less-invasive surgical approaches that may reduce recovery time for children with congenital heart disease who require these assist devices.

Using them in kids comes with added challenges, however. Often pediatric cardiologists have to be creative in how to make them work for smaller patients, Dr. Berul notes. This reiterates the important point that simply applying an adult technology to a child isn’t the right approach. The subcutaneous defibrillator, for example, is still pretty large for a child’s body. Some studies also show these devices may not be as accurate in children as in adults.

Investigators in the Sheikh Zayed Institute working together with the cardiologists at Children’s National Hospital are focused on product development and commercialization of tools and techniques to allow percutaneous minimally-invasive placement of devices, taking advantage of the newest devices and surgical techniques as they develop.

In his presentation, Dr. Berul stressed that as the technology for adults advances, it creates an opportunity for pediatric cardiology, but only if the devices, and the techniques to place them, are specifically redesigned for pediatric application.

American Heart Association Scientific Sessions 2020
The Future is Now (or Coming Soon): Updates on New Technologies in Congenital Heart Care – On Demand Session
CH.CVS.715
9:00am – 10:00am
Fri, Nov 13  (CST)

coronavirus

Single institution study finds high rates of cardiac complications in MIS-C

coronavirus

At this year’s AHA Scientific Sessions, cardiologists from Children’s National Hospital presented a poster about an interesting finding in children with MIS-C.

During the height of the pandemic, researchers at Children’s National Hospital discovered that as many as one half of children diagnosed with multisystem inflammatory disease in children (MIS-C) at the hospital developed cardiac complications including coronary artery abnormalities, even when diagnosed and treated promptly.

The data was shared as part of a poster presentation at the American Heart Association Scientific Sessions in November 2020. Though analysis was limited to the data from one institution’s confirmed MIS-C cases, the findings are significant enough to warrant further study.

Interestingly, the authors noted that the high rate of cardiac complications far exceeds the rate of similar issues in children with Kawasaki disease — another pediatric inflammatory syndrome that shares many common symptoms with MIS-C. The two are so similar that immunomodulation therapies successfully deployed in children with MIS-C were based on those developed to treat Kawasaki disease.

Knowledge of common cardiac complications in Kawasaki disease also flagged the need for routine echocardiograms in patients with MIS-C, which helped identify the higher rates of cardiac complications seen in the MIS-C patient population.

“This finding, however, is another data point that shows how MIS-C and Kawasaki disease have some specific differences needing further study,” says Ashraf Harahsheh, M.D., a pediatric cardiologist at Children’s National Hospital who studies Kawasaki disease and the first author on the new study.

“Previous clinical advancements made in Kawasaki disease set the stage for our response to MIS-C early on,” he said. ”Now we also need to understand MIS-C as its own syndrome so we can better address what we are seeing in this patient population,” he says.

While most of the cardiac findings resolved during follow up, long-term studies are needed to determine if the cardiac abnormalities are associated with major cardiac events later.

“This work will help inform the community of the importance of diagnosing children with MIS-C promptly and following clinical guidelines for necessary tests and treatments once MIS-C is diagnosed,” Harahsheh concludes.

Next, the research team plans to take a deep dive into patient demographics as well as findings from clinical, laboratory and electrocardiogram data for children who developed cardiac complications with MIS-C. The goal will be to refine treatment algorithms and potentially identify a subgroup of patients who may require different or more intense therapy to prevent cardiac complications.

American Heart Association Scientific Sessions 2020 Poster Session
Cardiac Complications of SARS CoV-2 Associated Multi-System Inflammatory Syndrome in Children (MIS-C)
P1306
9:00am – 10:00am
Fri, Nov 13 (CST)

EEG with electrical activity of abnormal brain

Speckle tracking echo reveals possible biomarker for SUDEP risk

EEG with electrical activity of abnormal brain

A study published in the journal Epilepsia used speckle tracking echocardiography to detect subtle changes in heart function found in pediatric patients with refractory epilepsy when compared to controls. Children with refractory epilepsy had impaired systolic ventricular strain compared to controls, not correlated to epilepsy history. These differences in ventricular function may be a biomarker that can indicate someone with epilepsy is at higher risk for Sudden Unexpected Death in Epilepsy (SUDEP).

Speckle tracking echocardiography is a non-invasive technique where software automatically identifies and tracks individual “speckles” of the myocardial wall on a routine echocardiogram in order to directly quantify the extent of contraction.

The study’s first authors, John Schreiber, M.D., medical director of Electroencephalography (EEG) and director of the Epilepsy Genetics program, and Lowell Frank, M.D., advanced imaging cardiologist and director of the Cardiology Fellowship Training program, both at Children’s National Hospital, answered some questions about the study findings.

Why is this important work?

Sudden unexpected death in epilepsy (SUDEP) is a rare but devastating consequence of epilepsy. Some of the proposed mechanisms of SUDEP implicate brain stem, cardiac and respiratory pathways.

This study identified alterations in ventricular function that may serve as one potential biomarker for SUDEP risk that can be evaluated non-invasively and regularly.

How will this work benefit patients?

Identification of children or adults with markedly impaired ventricular strain or diastolic function may provide the opportunity to implement a targeted treatment or monitoring strategy to prevent SUDEP.

What did you find that excites you? What are you hoping to discover?

These differences in cardiac strain were true for all patients with refractory epilepsy as a whole, not one particular group. This suggests that refractory convulsive epilepsy itself, rather than other patient-specific factors, produces these changes. Thanks in part to a grant from the Dravet Syndrome Foundation, the team is currently examining a cohort of patients with epilepsy due to pathogenic variants in sodium channel genes, SCN1A and SCN8A, to determine if these patients have greater degrees of impaired cardiac strain. SCN1A and SCN8A are also expressed in the heart, and patients have a considerably higher risk of SUDEP. It will be particularly exciting to examine for differences in specific genetic epilepsies.

How is this work unique?

Strain has been evaluated in many disease states in adult and pediatric populations and may be more sensitive to early myocardial damage than traditional measures of systolic and diastolic function. Children’s National Hospital has been an innovator in using speckle tracking echocardiography and similar techniques to evaluate subtle changes in heart function. This study is a great example of collaboration between The Comprehensive Pediatric Epilepsy Program and the Children’s National Heart Institute that is driving innovative research at Children’s National Hospital.

Research & Innovation Campus

Boeing gives $5 million to support Research & Innovation Campus

Research & Innovation Campus

Children’s National Hospital announced a $5 million gift from The Boeing Company that will help drive lifesaving pediatric discoveries at the new Children’s National Research & Innovation Campus.

Children’s National Hospital announced a $5 million gift from The Boeing Company that will help drive lifesaving pediatric discoveries at the new Children’s National Research & Innovation Campus. The campus, now under construction, is being developed on nearly 12 acres of the former Walter Reed Army Medical Center. Children’s National will name the main auditorium in recognition of Boeing’s generosity.

“We are deeply grateful to Boeing for their support and commitment to improving the health and well-being of children in our community and around the globe,” said Kurt Newman, M.D., president and CEO of Children’s National “The Boeing Auditorium will help the Children’s National Research & Innovation campus become the destination for discussion about how to best address the next big healthcare challenges facing children and families.”

The one-of-a-kind pediatric hub will bring together public and private partners for unprecedented collaborations. It will accelerate the translation of breakthroughs into new treatments and technologies to benefit kids everywhere.

“Children’s National Hospital’s enduring mission of positively impacting the lives of our youngest community members is especially important today,” said Boeing President and CEO David Calhoun. “We’re honored to join other national and community partners to advance this work through the establishment of their Research & Innovation Campus.”

Children’s National Research & Innovation Campus partners currently include Johnson & Johnson Innovation – JLABS, Virginia Tech, the National Institutes of Health (NIH), Food & Drug Administration (FDA), U.S. Biomedical Advanced Research and Development Authority (BARDA), Cerner, Amazon Web Services, Microsoft, National Organization of Rare Diseases (NORD) and local government.

The 3,200 square-foot Boeing Auditorium will be the focal point of the state-of-the-art conference center on campus. Nationally renowned experts will convene with scientists, medical leaders and diplomats from around the world to foster collaborations that spur progress and disseminate findings.

Boeing’s $5 million commitment deepens its longstanding partnership with Children’s National. The company has donated nearly $2 million to support pediatric care and research at Children’s National through Chance for Life and the hospital’s annual Children’s Ball. During the coronavirus pandemic, Boeing fabricated and donated 2,000 face shields to help keep patients and frontline care providers at Children’s National safe.

NCC-PDI device competition

Medical device competition announces six winners to share in $250K

Judges award grants for pediatric medical devices that address cardiovascular, NICU, and orthopaedic and spine device innovations.

Yves d'Udekem

Yves d’Udekem, M.D., Ph.D., joins Children’s National as Cardiac Surgery Chief

Yves d’Udekem, M.D., Ph.D., a pediatric cardiac surgeon recognized for expertise in the most challenging procedures for newborns and children with complex congenital heart disease, has joined Children’s National Hospital as chief of Cardiac Surgery and co-director of the Children’s National Heart Institute.

“Children’s National has the cases and expertise I was looking for,” he says. “Even better, when you visit it’s clear that the entire Heart Institute team is energetic about working together. They’re constantly seeking better ways to do this work and improve how we care for children and their families.”

Dr. d’Udekem comes to Children’s National from The Royal Children’s Hospital in Melbourne, Australia, an institution that has led the advancement of congenital heart disease care and research, performing more than 500 surgical procedures with cardiopulmonary bypass each year.

He has a broad spectrum of pediatric cardiac surgery expertise, with special emphasis in single ventricle congenital heart defects, when one lower chamber of the heart does not develop. One area of his research portfolio includes clinical research into long-term quality of life for people who had Fontan procedures — a critical surgical approach to adapt blood flow for people born with single ventricle heart disease. He has additional expertise in valve repair, artificial hearts and other cardiac assist devices.

“Sometimes it seems like I’ve been born and put on this earth for that single purpose — I have to bring life to patients with single ventricle hearts or assist devices,” he says. He describes his path to pediatric cardiac surgery as serendipity, “It’s more like pediatric cardiac surgery chose me.”

“It is an honor to welcome Yves d’Udekem to the Children’s National Heart Institute,” says David Wessel, M.D., executive vice president and chief medical officer of Hospital and Specialty Services at Children’s National. “He is a surgeon, physician and leader of the highest caliber. I can say without hesitation that Yves’ leadership of our cardiac surgery team will change the lives of hundreds, if not thousands, of children and adults with congenital heart disease.”

In preparation for Dr. d’Udekem’s arrival, the Children’s National Heart Institute and hospital leadership created a framework plan for success that will build on the legacy of excellence established by Richard Jonas, M.D. Dr. Jonas, a world leader in congenital heart surgery who has made significant clinical and academic advances in the field, will continue his award-winning laboratory-based research at Children’s National on neurodevelopmental outcomes for children with congenital heart disease.

Dr. d’Udekem is Belgian-born with Canadian and Australian citizenship. He received his early training in Belgium and Toronto. As an attending cardiac surgeon in Belgium, he operated on both adults and children with congenital heart disease. Dr. d’Udekem then worked with internationally recognized heart surgeon Marc de Leval, M.D., FRCS, and others in London to train in congenital heart surgery at the Great Ormond Street Hospital for Children. From there, he was recruited to The Royal Children’s Hospital in Melbourne, Australia, where he has been ever since.

Dr. d’Udekem has more than 350 research publications and has obtained more than $7 million in grant funding in the past five years for work to create the first research network of Australian children and adults who have undergone the Fontan procedure.

He started seeing patients at Children’s National in mid-September.

mother measuring sick child's temperature

Connections between Kawasaki disease and MIS-C

mother measuring sick child's temperature

A new review article enumerates some key similarities and differences between MIS-C and Kawasaki disease.

Since May 2020, there has been some attention in the general public and the news media to a specific constellation of symptoms seen in children with COVID-19 or who have been exposed to COVID-19. For a time, headlines even called it a “Kawasaki-like” disease. At first glance, both the symptoms and the effective treatments are remarkably similar. However, a new review published in Trends in Cardiovascular Medicine finds that under closer scrutiny, the two conditions have some interesting differences as well.

“At the beginning of this journey, we thought we might be missing actual cases of Kawasaki disease because we identified a few patients who presented late and developed coronary artery abnormalities,” says Ashraf Harahsheh, M.D., senior author of the review article, “Multisystem inflammatory syndrome in children: Is there a linkage to Kawasaki disease?” and a cardiologist at Children’s National Hospital. “But as time passed, children exposed to COVID-19 started to present with a particular constellation of symptoms that actually had some important similarities and distinctions from Kawasaki.”

Similarities between Kawasaki disease and MIS-C

Both disease patterns seem to have a common trigger that provokes the inflammatory cascade reaction in genetically susceptible children, the authors write. However, there is also early evidence that children with each disease have different genetic markers, meaning different populations are genetically susceptible to each disease.

Additionally, the authors found that the massive activation of pro-inflammatory cytokines seen in MIS-C, also known as a “cytokine storm,” overlaps with a similar occurrence seen in Kawasaki disease, adult COVID-19 patients, toxic shock syndrome and some other viral infections.

Primary differences between Kawasaki disease and MIS-C

Overall, when compared to Kawasaki disease, children with MIS-C tend to:

  • Present at an older age
  • Have a more profound form of inflammation
  • Have more gastrointestinal manifestation
  • Show different laboratory findings
  • Have greater risk of left ventricle dysfunction and shock

Further study of both Kawasaki and MIS-C needed

Despite noted differences, the authors are also careful to credit the documented similarities between Kawasaki disease and MIS-C as a key to the quick identification of the new syndrome in children. The study of Kawasaki disease also gave clinicians a valid basis to begin developing diagnostic recommendations and treatment protocols.

The review’s first author Yue-Hin Loke, M.D., who is also a cardiologist at Children’s National, says, “The quick recognition of MIS-C is only possible because of meticulous research conducted by Dr. Tomisaku Kawasaki, who recently passed away on June 5th, 2020. Even though some aspects of both are still shrouded in mystery, the previous research and clinical advancements made in Kawasaki disease set the stage for our immediate response to MIS-C.”

“Previous research provided key information for cardiologists facing this new syndrome, including the necessity of routine echocardiograms to watch for coronary artery abnormalities (CAAs) and for use of  intravenous immunoglobulin (IVIG) to mitigate  the development of CAAs,” says Charles Berul, M.D., chief of Cardiology at Children’s National and a co-author. “Both of these factors have played a key role in reducing the mortality of MIS-C to almost zero.”

The authors note that more research is needed to understand both Kawasaki disease and the specifics of MIS-C, but that what is learned about the mechanisms of one can and should inform study and treatment of the other. And in the meantime, caution and continued surveillance of these patients, especially with respect to coronary artery and myocardial function, will continue to improve the long-term outcomes for both syndromes.

telemedicine control room

Telehealth and AI reduce cardiac arrest in the cardiac ICU

telemedicine control room

The telehealth command center located a few steps away from the cardiac ICU at Children’s National Hospital.

The cardiac critical care team at Children’s National Hospital has developed an innovative Tele-Cardiac Critical Care model aiming to keep constant watch over the most fragile children with critical heart disease in the cardiac ICU. The system combines traditional remote monitoring and video surveillance with an artificial intelligence algorithm trained to flag early warning signs that a critically ill infant may suffer a serious event like cardiac arrest while recovering from complex cardiac surgery. This second set of eyes helps bedside teams improve patient safety and quality of care.

These high risk post-operative patients are often neonates or small infants born with the most complex and critical congenital heart diseases that require surgery or interventional cardiac catheterization in their first days or weeks of life. At these early stages after crucial cardiac surgery, these patients can decompensate dangerously fast with few outward physical symptoms.

The AI algorithm (T3) monitors miniscule changes in oxygen delivery and identifies any mismatch with a child’s oxygen needs. It also tracks and displays small changes in vital sign trends that could lead to a serious complication. The cardiac ICU command center staff then analyzes additional patient data and alerts the bedside team whenever needed.

The Tele-Cardiac Critical Care program started two years ago. In that time, the program has contributed to a significant decrease in post-operative cardiac arrest for this patient population.

“It’s easy to see how a model  like this could be adapted to other critical care scenarios, including our other intensive care units and even to adult units,” says Ricardo Munoz, M.D., chief of Cardiac Critical Care and executive director of Telehealth. It allows the physicians and nurses to keep constant watch over these fragile patients without requiring a physician to monitor every heartbeat in person for every patient at every hour of the day to maintain optimal outcomes for all of them.”

Dr. Munoz and Alejandro Lopez-Magallon, M.D., medical director of Telehealth and cardiac critical care specialist, presented data from the pilot program at the American Telemedicine Association’s virtual Annual Meeting on June 26, 2020.

doctors operating

U.S. DoD awards $2M for study to protect neurological function after cardiac surgery

doctors operating

A collaboration between clinical and basic science researchers including Drs. Ishibashi, Hashimoto-Torii, Jonas, and Deutsch, seeks to to understand how caspase enzyme activation plays a role in the development of fine and gross motor skills in children who underwent cardiac surgery for CHD repair.

The U.S. Department of Defense has awarded $2 million to Children’s National Hospital to study how a family of protease enzymes known as caspases may contribute to brain cell degeneration when activated by prolonged anesthesia and cardiopulmonary bypass during cardiac surgery for congenital heart disease.

This U.S. Army Medical Research Acquisition Activity Award, Anesthesia Neurotoxicity in Congenital Heart Disease, is led by principal investigator Nobuyuki Ishibashi, M.D., with both clinical and basic science co-investigators including Kazue Hashimoto-Torii, Ph.D., (Neuroscience), Richard Jonas, M.D., (Cardiovascular Surgery) and Nina Deutsch, M.D., (Anesthesiology).

While the specific cellular and molecular mechanisms of how anesthesia and cardiac surgery impact cortical development are poorly understood, both seem to impact brain growth and development in young children. The most common neurologic deficit seen in children after CHD surgical repair is the impairment of fine and gross motor skills.

Both anesthetic agents and inflammation like that seen as a result of cardiopulmonary bypass have also been shown to contribute to the activation of a specific group of enzymes that play an essential role in the routine (programmed) death of cells: caspases. However, recent pre-clinical research shows that these enzymes may also contribute to other alterations to cells beyond cell death, including making changes to other cell structures. In pre-clinical models, these changes cause impairments to fine and gross motor skills – the same neurological deficits seen in children with CHD who have undergone procedures requiring prolonged anesthesia and cardiopulmonary bypass.

The research team hypothesizes that caspases are extensively activated as a result of cardiac surgery and while that activation is rarely causing reduced numbers of neurons, the changes that caspase enzymes trigger in neurons are contributing to neurological deficits seen in children with CHD after surgery.

While the study focuses specifically on the impacts of cardiac surgery for correction of a heart defect, the findings could have major implications for any pediatric surgical procedure requiring prolonged anesthesia and/or cardiopulmonary bypass.

US News Badges

Children’s National ranked a top 10 children’s hospital and No. 1 in newborn care nationally by U.S. News

US News Badges

Children’s National Hospital in Washington, D.C., was ranked No. 7 nationally in the U.S. News & World Report 2020-21 Best Children’s Hospitals annual rankings. This marks the fourth straight year Children’s National has made the list, which ranks the top 10 children’s hospitals nationwide.

In addition, its neonatology program, which provides newborn intensive care, ranked No.1 among all children’s hospitals for the fourth year in a row.

For the tenth straight year, Children’s National also ranked in all 10 specialty services, with seven specialties ranked in the top 10.

“Our number one goal is to provide the best care possible to children. Being recognized by U.S. News as one of the best hospitals reflects the strength that comes from putting children and their families first, and we are truly honored,” says Kurt Newman, M.D., president and CEO of Children’s National Hospital.

“This year, the news is especially meaningful, because our teams — like those at hospitals across the country — faced enormous challenges and worked heroically through a global pandemic to deliver excellent care.”

“Even in the midst of a pandemic, children have healthcare needs ranging from routine vaccinations to life-saving surgery and chemotherapy,” said Ben Harder, managing editor and chief of Health Analysis at U.S. News. “The Best Children’s Hospitals rankings are designed to help parents find quality medical care for a sick child and inform families’ conversations with pediatricians.”

The annual rankings are the most comprehensive source of quality-related information on U.S. pediatric hospitals. The rankings recognize the nation’s top 50 pediatric hospitals based on a scoring system developed by U.S. News. The top 10 scorers are awarded a distinction called the Honor Roll.

The bulk of the score for each specialty service is based on quality and outcomes data. The process includes a survey of relevant specialists across the country, who are asked to list hospitals they believe provide the best care for patients with the most complex conditions.

Below are links to the seven Children’s National specialty services that U.S. News ranked in the top 10 nationally:

The other three specialties ranked among the top 50 were cardiology and heart surgery, gastroenterology and gastro-intestinal surgery, and urology.

Nobuyuki Ishibashi

R01 grant funds white matter protection study for congenital heart disease

Nobuyuki Ishibashi

Nobuyuki Ishibashi, M.D., is the principal investigator on a $3.2 million NIH R01 to study white matter growth and repair in utero for fetal brains affected by congenital heart disease.

Many of the neurological deficits seen in children with congenital heart disease (CHD) are related to abnormal white matter development early in life caused by reduced oxygen supply to the brain while in utero. Children with immature white matter at birth also commonly sustain additional white matter injuries following cardiac surgery.

The NIH recently awarded a prestigious R01 grant totaling more than $3.2 million to a collaborative project led by the Center for Neuroscience Research, the Sheikh Zayed Institute for Pediatric Surgical Innovation and the Children’s National Heart Institute at Children’s National Hospital as well as MedStar Washington Hospital Center.

The research, titled “White matter protection in the fetus with congenital heart disease,” looks specifically at whether providing a supplemental amount of the naturally occurring tetrahydrobiopterin (BH4) for pregnant women could rescue white matter development of fetuses with congenital heart disease whose brains aren’t receiving enough oxygen – or suffering from hypoxic-ischemic events.

Previous preclinical studies have shown that this lack of oxygen depletes the brain’s natural BH4 level, and the researchers hypothesize that BH4 levels play a critical role in the growth and development of white matter in the fetal brain by triggering key cellular/molecular processes. Specifically, the study will focus on three aims:

  1. Establish in a preclinical model the optimal protective regiment for women pregnant with a fetus who has CHD to receive BH4.
  2. Determine the appropriate approach to deliver BH4 to this population
  3. Leverage genetic tools and biochemical techniques in the laboratory to better understand where and how BH4 levels play a role in the growth (or lack thereof) of oligodendrocytes—the primary cells of white matter.

This laboratory-based work is the first step to determining if the neurodevelopment of babies born with CHD can be preserved or recovered by addressing key brain development that occurs before the baby is even born. Findings related to congenital heart disease may also translate to other populations where white matter development is affected by hypoxia-ischemia, including premature infants.

The project is led by principal investigator Nobuyuki Ishibashi, M.D., with co-investigators Vittorio Gallo, Ph.D., Joseph Scafidi, D.O., and Mary Donofrio, M.D. as well as colleagues at MedStar Washington Hospital Center.