Tag Archive for: critical congenital heart disease

Cayden rides a horse with her father

Earliest hybrid HLHS heart surgery kids thrive 5 years later

Cayden rides a horse with her father

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

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

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

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

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

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

Read the rest of Cayden’s story here.

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

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

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

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

What this means

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

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

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

Why it matters

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

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

Children’s National Hospital leads the way

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

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

x-ray of child with congenital heart disease

Cell therapy research for neuroprotection in congenital heart disease receives another $3.3 million from NIH

x-ray of child with congenital heart disease

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

The research lab of Nobuyuki Ishibashi, M.D., at Children’s National Hospital, recently received $3.3 million in additional funding for research into cell therapy for neuroprotection in children with congenital heart disease. The new support comes from the National Heart, Lung and Blood Institute (NHLBI) of the National Institutes of Health.

The research goal

The overarching goal of the award is to establish detailed molecular signatures from critical cell populations for tissue repair and regeneration at single cell resolution after bone marrow-derived mesenchymal stromal cell (BM-MSC) delivery. The team has shown cellular, structural and behavioral improvements in pre-clinical models after delivery of BM-MSCs through cardiopulmonary bypass for children with congenital heart disease. However, the mechanisms underlying the therapeutic action of BM-MSCs still remain largely unknown. This R01 renewal will address the key knowledge gap.

Why it matters

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

The Ishibashi lab has demonstrated the efficacy and utility of using cardiopulmonary bypass to deliver BM-MSCs  to improve neurological impairments in children undergoing surgery for congenital heart disease. Most notably, this included development of a phase 1 clinical trial, MeDCaP, at Children’s National.

The big picture

Together with the ongoing clinical trial established from the previous award, identifying molecular signatures of BM-MSC treatment and mining specific BM-MSC exosomes for unique cardiopulmonary bypass pathology will significantly improve understanding of this cell-based treatment. This work will also provide a new therapeutic paradigm for potential cell-free MSC-based therapies for neuroprotection in children with congenital heart disease.

doctors doing heart surgery

Innovative hypoplastic left heart syndrome treatment offers hope for highest risk children

doctors doing heart surgery

A recently published study in the Journal of Thoracic and Cardiovascular Surgery is a unique report of outcomes for infants treated using a staged surgical approach such as the “hybrid strategy.”

Adopting a staged surgical strategy as the standard of care for medically fragile children with hypoplastic left heart syndrome (HLHS), a critical congenital heart defect, shows promise as an alternative care path for those who may not be ideal candidates for open heart surgery immediately after birth.

A recently published study in the Journal of Thoracic and Cardiovascular Surgery is a unique report of outcomes for infants treated using a staged surgical approach such as the “hybrid strategy.” This initially less-invasive technique involves the placement of small bands on both lung vessels, with or without the placement of a stent on the ductus arteriosus, as the first stage in surgical palliation.

The study reports results from applying this hybrid approach as a bridge to either a delayed Norwood operation or a comprehensive stage II operation. Over 3.5 years, 30 patients with HLHS were considered very high risk for surgery based on their preoperative risk factors such as low birth weight and/or gestational age, shock, and other medical conditions. During that time, the overall survival rate for this group was 70 percent. In the past, using traditional approaches, the survival chance for infants with HLHS and these high-risk factors was extremely limited.

Why it matters

This new surgical strategy gives the baby extra time to grow and allows doctors to collect detailed analysis of potentially treatable accompanying conditions. Furthermore, high-risk babies recover from birth trauma and have the chance to continue developing crucial organs before undergoing more traditional procedures for HLHS that require open-heart surgery with cardiopulmonary bypass. It also allows surgeons to make an individualized risk assessment for which surgical step should be taken next, replacing the historical “one size fits all” operative pathway for HLHS. The traditional operative pathway for HLHS is a series of three open-heart surgical procedures: the traditional Norwood operation, the bidirectional Glenn and the Fontan.

Advancing the standard of care for HLHS patients beyond the current best practice approach to improve outcomes for more newborns has been slow for several reasons, the authors note. One main reason is that performing a hybrid procedure on these particularly fragile infants requires advanced devices and additional technical expertise. As one example, the authors note that until recently, there was no stent available in the appropriate sizes and with the right material properties to work within such a tiny ductus arteriosus. However, case-by-case expanded access approval by the FDA has brought a new stent designed specifically for this use from Europe to the U.S. for the first time.

What they’re saying

“The Norwood operation revolutionized the care of children with HLHS in the 1980s and gave them a chance for survival,” says Can Yerebakan, M.D., senior author of the study and cardiac surgeon at Children’s National who oversees the hybrid program alongside Joshua Kanter, M.D., director of Interventional Cardiology. “This staged decision-making strategy may give the same kind of hope and offers an alternative pathway of care for high-risk patients who would otherwise have a dismal prognosis and extremely low chance   of survival in the newborn period. The success in these cases is, however, based on a multidisciplinary team approach.”

What’s next?

“This strategy not only shows promise for improved short-term survival in high-risk patients, but also boasts the potential to convert some patients to two-chamber circulation instead of one, which our team has done with 100% survival,” says Nicolle Ceneri, M.D., first author of the study and pediatric resident at Children’s National. “As time goes on, we are eager to discover how the use of this approach during such a tenuous period impacts the long-term outcomes for these children and their quality of life.”

Read about the smallest baby born with HLHS to survive to 18 months, who was treated using this hybrid surgical approach at Children’s National Hospital.

flow chart of pulse ox study

Newborn screening for critical congenital heart disease serves as vital safety net

One of the nation’s longest-running newborn screening programs for critical congenital heart disease (CCHD) finds that screening continues to serve as a necessary tool to help identify every child with CCHD — even in states where the majority of babies are diagnosed before birth.

The screening program study findings were published in Pediatrics. The data is some of the first to provide long-term evidence for using pulse oximetry to screen newborns for critical congenital heart disease 24 hours after birth. This screening test was added to the Department of Health and Human Services Recommended Uniform Screening Panel in 2011 and is now required in all 50 states.

“This study reinforces why pulse oximetry screening for CCHD is an important tool in our arsenal to identify and treat critical congenital heart disease, and other conditions that affect the flow of oxygen throughout the body, as soon as possible,” says Bryanna Schwarz, M.D., a cardiology fellow at Children’s National Hospital and lead author. “We know that prompt, early detection and swift intervention is crucial to positive long-term outcomes for these kids.”

The team looked at the data and outcomes for all babies born throughout eight years at Holy Cross Hospital in suburban Maryland, one of the first community birthing hospitals in the country to routinely perform the screening. Over the eight-year period, 64,780 newborns were screened at the site. Of those:

  • Thirty-one failed the screening, and every baby who failed was found to have congenital heart disease or another important medical condition.
  • Twelve of the failures (38.7%) were babies with critical congenital heart disease who were not previously identified by prenatal detection.
  • Nine others (29%) had a non-critical congenital heart condition.
  • Ten additional babies (32%) had a non-cardiac condition.

The authors note that the 12 newborns with CCHD identified through pulse oximetry screening are noteworthy because they represent critical congenital heart disease cases that are not found before birth in the state of Maryland, where rates of prenatal diagnosis are relatively high. The finding indicates that screening after birth continues to play a critical role in ensuring every baby with critical congenital heart disease is identified and treated as quickly as possible.

“Holy Cross Health and Children’s National have had a decades-long relationship, as we mutually care for women and infants throughout the region. With Children’s National having the U.S. News & World Report #1 ranking Neonatology service in the nation and Holy Cross Hospital being among the top 10 hospitals for the number of babies delivered each year, we are honored to be leading together the great work that is being done to serve our health care community,” says Ann Burke, M.D., vice president of Medical Affairs at Holy Cross Hospital. “We are committed to continuing to do our part to care for women and infants, as well as contribute to the national landscape for neonatal care. We are delighted in the outcomes we have seen and look forward to continued advancement.”

In this study, infants who did not have critical congenital heart disease were considered “false positives” for CCHD. Still, every one of them was found to have another underlying condition, including non-critical congenital heart disease or non-cardiac conditions (such as sepsis and pneumonia) that would also require monitoring and treatment.

The researchers also ran a projection of recently recommended updates to the screening protocol, which include removing a second re-screen after a newborn fails the initial test, to look at whether removing the second rescreen to verify results would decrease accuracy. While the false positive rate did increase slightly from .03% to .04%, eliminating a second re-screen allowed the newborns who were identified to receive crucial care sooner without having to wait an additional hour for one more test to verify their condition.

“It’s time to stop asking if pulse oximetry is a necessary tool to detect critical heart disease in babies,” says Gerard Martin, M.D., M.A.C.C., senior author of the study and C.R. Beyda Professor of Cardiology at Children’s National Hospital. “Our focus now should be on making evidence-based refinements to the screening protocol based on collected data to ensure the process is simple, can be performed consistently and provides as accurate results as possible.”