Two CHOP Teams Awarded Funds to Study Single Ventricle Congenital Heart Disease

Two research teams in the Cardiac Center at Children’s Hospital of Philadelphia (CHOP) have been awarded research grants to study single ventricle congenital heart disease (SVCHD), a severe form of cardiac malformation in which only one of the four chambers of the heart works properly. Provided by Additional Ventures through its Single Ventricle Research Fund, the grants will accelerate research and improve care for those with single ventricle heart defects.

Jack Rychik, MD Jack Rychik, MD, the Robert & Dolores Harrington endowed chair in cardiology and Director of CHOP’s Fontan Rehabilitation, Wellness, Activity and Resilience Development (FORWARD) Program, and Liming Pei, PhD, Associate Professor of Pathology and Laboratory Medicine at the CHOP Center for Mitochondrial and Epigenomic Medicine and Cardiovascular Institute, will study Fontan associated liver disease (FALD), which can limit survival and increase morbidity in SVCHD patients. Those with SVCHD undergo a surgical procedure known as a Fontan operation, which is a solution but far from a complete cure for this condition. Although 80% of those born with SVCHD can now survive to adulthood with a Fontan circulation, they often face new life-threatening complications. FALD is one of the most prevalent and challenging of these complications.

Pei Liming, PhD Despite its prevalence, the fundamental biology and molecular underpinnings of FALD are not well understood. Through analysis of liver specimens using sophisticated techniques such as single-nucleus RNA gene sequencing, Dr. Rychik and Dr. Pei plan to generate a comprehensive “multi-omics” atlas for FALD, revealing the fundamental biology of, and new insights into, the condition. They will also demonstrate the value of this atlas by identifying and validating new therapeutic targets for treating FALD. This research represents a unique collaboration between basic scientists and clinicians focused on complications of the Fontan circulation and reflects an innovative approach to solving the challenges of this population.

Matthew A. Jolley, MD Matthew A. Jolley, MD, an attending anesthesiologist and cardiologist at with CHOP, will lead a team of researchers in investigating the application of computational modeling of atrioventricular valve failure (AVF) in SVCHD patients with a complete atrioventricular canal defect (SV-AVC). AVF is associated with a 2.5-fold increase in risk of heart failure or death in SVCHD patients, and SV-AVC patients are at the highest risk for AVF. More than 50% of SV-AVC patients suffer from AVF in the first two decades of life, and outcomes of SV-AVC valve repair are poor. Using three-dimensional echocardiography (3DE) and computational modeling tools, the researchers will investigate structural factors in the heart that exacerbate AVF and perform “virtual surgery” to repair these factors. Their aim is to develop patient-specific computational modeling that would ultimately improve outcomes in patients with SV-AVC.