Postnatal hypoxemia, cardiac immaturity, and the impact on surgical recovery

The National Heart, Lung, and Blood Institute awarded Children's Research Institute $1,818,088 on July 15, 2026, under the Cardiovascular Diseases Research program (CFDA 93.837) to investigate how postnatal hypoxemia—reduced blood oxygen levels present in cyanotic congenital heart disease—impacts cardiac maturation and surgical recovery outcomes in pediatric patients.

The project will examine the interaction between hypoxemia, myocardial immaturity, and postoperative complications through three research aims: determining how postnatal hypoxemia affects the biological age of developing cardiomyocytes; evaluating the direct effects of hypoxemia on reoxygenation injury and myocardial drug responsiveness; and investigating the clinical impact of hypoxemia on cardiac function in pediatric congenital heart disease patients. The research employs complementary experimental animal models, human biological samples, and patient biomonitoring data to address the urgent need for improved postoperative outcomes in pediatric congenital heart disease, where 25–80% of patients experience postoperative morbidity including neurological injury, arrhythmias, and low cardiac output syndrome.

Performance occurs in Washington, DC from July 15, 2026 through June 30, 2028. This is a Project Grant, the standard assistance type for investigator-initiated research through the National Institutes of Health.

Abstract

Congenital heart disease (CHD) is the most common birth defect, affecting 1% of live births. Approximately 25% of CHD cases are considered critical and require surgical correction within the first year of life. Nearly 25-80% of pediatric CHD patients experience postoperative morbidity, including neurological injury, arrhythmias, and low cardiac output syndrome (LCOS). Of those patients with at least one complication, the discharge mortality rate increases from 2% to 24%. As such, there is an urgent need to identify areas of improvement for better postoperative outcomes. This is particularly important for patients with cyanotic CHD lesions, which reduce blood oxygen levels and cause tissue hypoxemia. Cyanotic CHD patients have an 8-fold increased risk of death and ~40% of patients develop heart failure during childhood. We hypothesize that hypoxemia - as observed in cyanotic CHD - impacts the biological age of cardiomyocytes, resulting in inefficient intracellular calcium handling, reduced adrenergic signaling, and inadequate antioxidant reserve. As a result, the hypoxic heart is more sensitive to reoxygenation injury during surgery, more vulnerable to contractile dysfunction, and less responsive to drugs frequently used to treat LCOS. We will use a complementary set of experimental animal models, human biological samples, and patient biomonitoring data to assess the interaction between hypoxemia, myocardial immaturity, and surgical recovery. The following aims are proposed: aim 1: determine the impact of postnatal hypoxemia on the biological age of developing cardiomyocytes. Aim 2: evaluate the direct effects of postnatal hypoxemia on reoxygenation injury and myocardial drug responsiveness. Aim 3: investigate the clinical impact of postnatal hypoxemia on cardiac function in pediatric CHD patients. Our study will utilize collaborative biobanking efforts to collect and store biospecimens from children with CHD. Results of our transcriptomic and biomarker study will be available to the research community - which can provide the framework for new pediatric computational models for cardiac research and/or the identification of novel biomarkers to better predict disease trajectory and/or patient risk stratification. Further, the results of our study can serve as the foundation for future clinical trials to assess myocardial preservation techniques, drug efficacy, and postoperative outcomes in children undergoing corrective heart surgery. Considering the variability in drug choice between cardiac surgical centers, the results of our work can inform and shift clinical practice to favor one medication over another for sensitive, cyanotic CHD patients. Since this project includes a highly innovative collaborative team of basic and clinical researchers, the results of our translational studies can have an immediate impact by refining the surgical/perfusion protocols and/or monitoring of specific patient groups at our institution.