An article published in the journal Cardiology in the Young provides a comprehensive timeline mapping the growth trajectory of cardiology and cardiac surgery at one of the nation’s oldest children’s hospitals — Children’s National Hospital in Washington, D.C.
Cardiology and cardiac surgery at Children’s National have grown exponentially in the nearly 80 years since the first heart-related surgery was recorded in 1942. Today, aligned with the growth trajectory of the hospital as it has evolved to become one of the top-ranked pediatric institutions in the country, the Children’s National Heart Institute has also evolved. In the last year, this included welcoming new Cardiac Surgery Chief, Yves d’Udekem, M.D., Ph.D.
The authors, Gerard Martin, M.D., M.A.C.C., C.R. Beyda Professor of Cardiology, and Richard Jonas, M.D., emeritus chief of Cardiac Surgery, both from Children’s National Hospital, note that this history of care has laid the groundwork for the Heart Institute to continue growing and caring for more neonates, infants, children and adults with congenital heart disease in the entire mid-Atlantic region and around the world.
The article features a timeline mapping the growth of cardiac care for neonates, children and adults at Children’s National Hospital.
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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.
“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.”
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.
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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.
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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.
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Children’s National Hospital announced that world-class surgeon Yves d’Udekem, M.D., Ph.D., will become the next Chief of Cardiac Surgery and Co-Director of the Children’s National Heart Institute this summer.
Dr. d’Udekem is Belgian-born with Canadian and Australian citizenship and 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 Laval, 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, an institution that has been a leader in advancing the field of congenital heart disease. In Melbourne, Dr. d’Udekem built an outstanding reputation for clinical excellence and an exceptional academic career. He has over 300 publications and is highly cited and respected. Dr. d’Udekem obtained more than $7 million in grant funding over the past five years as the creator and leader of the highly touted Fontan Registry.
The Children’s National Cardiology team and hospital leadership have built a framework for Dr. d’Udekem to succeed and advance the legacy that has been so successfully created in cardiac surgery by Richard Jonas, M.D. Dr. Jonas is a world leader in congenital heart surgery who made significant clinical and academic advances in the field and will continue his award-winning research career at Children’s National in the laboratory focusing on neurodevelopmental outcomes for children with heart disease.
Children’s National offers a comprehensive surgical program that includes a team of experienced surgeons performing the full range of procedures available for treatment of pediatric cardiac disease and congenital heart defects. The high volume program serves neonates through adults with congenital heart disease with particular attention to neurodevelopmental outcomes.
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The goal of the study will be to optimize brain development in babies with congenital heart disease (CHD) who sometimes demonstrate delay in the development of cognitive and motor skills.
An upcoming clinical trial at Children’s National Hospital will harness cardiopulmonary bypass as a delivery mechanism for a novel intervention designed to stimulate brain growth and repair in children who undergo cardiac surgery for congenital heart disease (CHD).
The NIH has awarded Children’s National $2.5 million to test the hypothesis that mesenchymal stromal cells (MSCs), which have been shown to possess regenerative properties and the ability to modulate immune responses in a variety of diseases, collected from allogeneic bone marrow, may promote regeneration of damaged neuronal and glial cells in the early postnatal brain. If successful, the trial will determine the safety of the proposed treatment in humans and set the stage for a Phase 2 efficacy trial of what could potentially be the first treatment for delays in brain development that happen before birth as a consequence of congenital heart disease. The study is a single-center collaboration between three Children’s National physician-researchers: Richard Jonas, M.D., Catherine Bollard, M.B.Ch.B., M.D. and Nobuyuki Ishibashi, M.D.
Dr. Jonas, chief of cardiac surgery at Children’s National, will outline the trial and its aims on Monday, November 18, 2019, at the American Heart Association’s Scientific Sessions 2019. Dr. Jonas was recently recognized by the Cardiac Neurodevelopmental Outcome Collaborative for his lifelong research of how cardiac surgery impacts brain growth and development in children with CHD.
Regenerative Cell Therapy in Congenital Heart Disease – Protecting the Immature Brain
Presented by Richard Jonas, M.D.
AHA Scientific Sessions
Session CH.CVS.608 Congenital Heart Disease and Pediatric Cardiology Seminar: A Personalized Approach to Heart Disease in Children
9:50 a.m. to 10:05 a.m.
November 18, 2019
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