The Cardiac Center at the Children’s Hospital of Philadelphia (CHOP) is leading pioneering research with grants aimed at improving outcomes for children with severe cardiac conditions. These efforts represent a comprehensive approach to advancing cardiac care from prenatal stages through childhood, potentially transforming treatment paradigms.
J. William Gaynor, MD, a surgeon in the Cardiac Center at CHOP, is spearheading a three-year research initiative with Boston Children’s Hospital and the University of Pennsylvania. The initiative is funded by a $660,000 grant from Additional Ventures' Single Ventricle Research Fund to develop therapies for fetuses with hypoplastic left heart syndrome (HLHS).
There are currently no treatments available during pregnancy to improve the health or survival of babies with HLHS, leaving families without options to reduce the risks before birth. However, a prior CHOP study showed that treatment of pregnant women with progesterone, a hormone important for brain development, lowered the risk of death for infants with HLHS from 20% to 7%. Researchers found the results promising and are seeking to better understand why progesterone was beneficial to design the best treatments for HLHS.
In addition to Gaynor’s team at CHOP, the research team will include Lauren Anton, PhD, Research Assistant Professor of Obstetrics and Gynecology at Penn and Sarah Morton, MD, PhD, Assistant Professor of Pediatrics at Harvard Medical School and will build on the prior study’s foundation. They proposed metabolomic, transcriptomic, and genetic studies using placenta, maternal/cord blood, and exome sequencing to identify mechanisms underlying the response to progesterone therapy in 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 research will focus on determining if alterations in placental progesterone metabolism are mechanistically associated with HLHS fetal and post-natal outcomes. The study will also evaluate the impact of common genetic variation on gestational age (GA) at birth, birthweight, and placental weight and efficiency in fetal congenital heart disease (CHD). Additionally, the team will identify transcriptional and cellular impacts of vaginal progesterone therapy.
The researchers hope their findings will help transform the paradigm for treating HLHS, allowing clinicians to take potentially lifesaving steps before a baby is born.
In a separate cardiac grant for $659,937, Wensi Wu, PhD, Research Assistant Professor in the Cardiovascular Institute at CHOP and the Department of Mechanical Engineering at the University of Pennsylvania, is leading a collaborative effort to address Atrioventricular valve (AVV) failure, a leading cause of complications in children with Fontan circulation. Wu partnered with Matthew A. Jolley, MD, an attending anesthesiologist and cardiologist at CHOP, and Alison M. Pouch, PhD, Assistant Professor of Bioengineering and Radiology at Penn.
As part of this effort, Dr. Wu and her research team will use a machine learning model to investigate the biomechanical mechanisms of AVVs in single ventricle patients with HLHS and unbalanced atrioventricular canal. The study will characterize variations in leaflet elastic properties in both healthy and diseased AVVs using ultrasound imaging. Longitudinal changes in leaflet biomechanics will also be examined to elucidate the mechanistic pathways driving progressive AVV deterioration.
“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.”
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The Cardiac Center at the Children’s Hospital of Philadelphia (CHOP) is leading pioneering research with grants aimed at improving outcomes for children with severe cardiac conditions. These efforts represent a comprehensive approach to advancing cardiac care from prenatal stages through childhood, potentially transforming treatment paradigms.
J. William Gaynor, MD, a surgeon in the Cardiac Center at CHOP, is spearheading a three-year research initiative with Boston Children’s Hospital and the University of Pennsylvania. The initiative is funded by a $660,000 grant from Additional Ventures' Single Ventricle Research Fund to develop therapies for fetuses with hypoplastic left heart syndrome (HLHS).
There are currently no treatments available during pregnancy to improve the health or survival of babies with HLHS, leaving families without options to reduce the risks before birth. However, a prior CHOP study showed that treatment of pregnant women with progesterone, a hormone important for brain development, lowered the risk of death for infants with HLHS from 20% to 7%. Researchers found the results promising and are seeking to better understand why progesterone was beneficial to design the best treatments for HLHS.
In addition to Gaynor’s team at CHOP, the research team will include Lauren Anton, PhD, Research Assistant Professor of Obstetrics and Gynecology at Penn and Sarah Morton, MD, PhD, Assistant Professor of Pediatrics at Harvard Medical School and will build on the prior study’s foundation. They proposed metabolomic, transcriptomic, and genetic studies using placenta, maternal/cord blood, and exome sequencing to identify mechanisms underlying the response to progesterone therapy in 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 research will focus on determining if alterations in placental progesterone metabolism are mechanistically associated with HLHS fetal and post-natal outcomes. The study will also evaluate the impact of common genetic variation on gestational age (GA) at birth, birthweight, and placental weight and efficiency in fetal congenital heart disease (CHD). Additionally, the team will identify transcriptional and cellular impacts of vaginal progesterone therapy.
The researchers hope their findings will help transform the paradigm for treating HLHS, allowing clinicians to take potentially lifesaving steps before a baby is born.
In a separate cardiac grant for $659,937, Wensi Wu, PhD, Research Assistant Professor in the Cardiovascular Institute at CHOP and the Department of Mechanical Engineering at the University of Pennsylvania, is leading a collaborative effort to address Atrioventricular valve (AVV) failure, a leading cause of complications in children with Fontan circulation. Wu partnered with Matthew A. Jolley, MD, an attending anesthesiologist and cardiologist at CHOP, and Alison M. Pouch, PhD, Assistant Professor of Bioengineering and Radiology at Penn.
As part of this effort, Dr. Wu and her research team will use a machine learning model to investigate the biomechanical mechanisms of AVVs in single ventricle patients with HLHS and unbalanced atrioventricular canal. The study will characterize variations in leaflet elastic properties in both healthy and diseased AVVs using ultrasound imaging. Longitudinal changes in leaflet biomechanics will also be examined to elucidate the mechanistic pathways driving progressive AVV deterioration.
“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.”
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