The Cardiac Center at Children’s Hospital of Philadelphia (CHOP) is advancing research into treatments for children with severe heart conditions, supported by new grants. These projects aim to improve care from prenatal stages through childhood and may change current treatment methods.
J. William Gaynor, MD, a surgeon in the Cardiac Center at CHOP, is leading a three-year study in collaboration with Boston Children’s Hospital and the University of Pennsylvania. The initiative has received $660,000 from Additional Ventures’ Single Ventricle Research Fund to develop therapies for fetuses diagnosed with hypoplastic left heart syndrome (HLHS).
Currently, no prenatal treatments exist to improve outcomes for babies with HLHS. Previous research at CHOP indicated that treating pregnant women with progesterone reduced infant mortality rates in HLHS cases from 20% to 7%. Researchers are now investigating why progesterone was effective in order to design better therapies.
Alongside Dr. Gaynor, the research team includes Lauren Anton, PhD, of Penn’s Department of Obstetrics and Gynecology, and Sarah Morton, MD, PhD, of Harvard Medical School. They plan to conduct metabolomic, transcriptomic, and genetic studies using placenta samples as well as maternal and cord blood. Their goal is to identify how progesterone therapy affects fetuses with HLHS.
“We will study placental, maternal, and fetal samples collected during our recent study to investigate how progesterone may improve placental function and thus survival in fetal HLHS. We will determine how progesterone treatment altered placental cells and will also test whether the infants who had the most benefit from progesterone had a different response compared to those who did not have a benefit,” said Gaynor. “These results will teach us about the role of progesterone during pregnancy, which will help us to identify new potential prenatal therapies for HLHS.”
The study will examine whether changes in placental progesterone metabolism relate directly to outcomes for fetuses with HLHS both before and after birth. It will also assess if common genetic variations affect gestational age at birth or birthweight among children with congenital heart disease.
In addition to this project, Wensi Wu, PhD—a research assistant professor at CHOP’s Cardiovascular Institute—received nearly $660,000 for work targeting Atrioventricular valve (AVV) failure in children living with Fontan circulation. Wu works jointly with Matthew A. Jolley, MD (CHOP), and Alison M. Pouch, PhD (University of Pennsylvania).
Dr. Wu’s team is developing a machine learning model designed to analyze biomechanical factors behind AVV failure in single ventricle patients such as those with HLHS or unbalanced atrioventricular canal defects. Using ultrasound imaging data collected over time, they hope to better understand how leaflet biomechanics change as valve deterioration progresses.
“Early diagnosis is essential to guide timely intervention and to ensure the long-term success of Fontan physiology. However, existing diagnostic approaches offer limited insight into the biomechanical factors that contribute to valve dysfunction,” said Wu. “Our collaborative initiative aims to address this critical gap by developing artificial intelligence-powered tools to enable noninvasive and real-time assessment of heart valve health across pediatric and adult populations.”
Both projects reflect ongoing efforts by CHOP researchers—and their partners—to find earlier interventions for serious pediatric cardiac conditions.
