Heart Institute Researchers Awarded Major Grants to Study Congenital Heart Defects

Shelley Miyamoto, MD and Stephanie Nakano, MD, were two of five research teams selected for a $13 million grant to study biological mechanisms of rare congenital heart defects. The American Heart Association and Additional Ventures are funding the research and selected the teams for their forward-thinking approaches to research using innovative methods to challenge current knowledge and theories in search of cures for single ventricle disease. Both doctors already have extensive experience studying single ventricle heart disease as well as treating pediatric cardiology patients.

Dr. Miyamoto is leading a study called “The DEFEND Trial: Dapagliflozin or Empagliflozin for Fontan Exercise, QOL and Ketone Body Levels.” Her team includes Roni Jacobsen, MD, an expert in exercise and adult congenital heart disease, and cardiac psychologist Sarah Kelly, PsyD.

The team is studying the use of two sodium-glucose co-transporter 2 (SGLT2) inhibitors used to treat diabetes and heart failure in adults to determine if these medications may also help teenagers and young adults with single ventricle disease. They hope to determine if the medications improve quality of life and the ability to exercise. People with single ventricle disease are often left out of studies of new medicines, so the DEFEND study will help address this disparity.

“Our goal is to advocate for the interests of patients with congenital heart disease and make sure they are part of studies on new and important treatments,” says Dr. Miyamoto. “These patients need and deserve special focus, and we're honored to have the chance to represent their needs through this new research project.”

Dr. Nakano is leading a study called “Consequences of Impaired T Cell Homeostasis in Single Ventricle Congenital Heart Disease.” Her team includes pediatric cardiologist Anastacia Garcia, PhD, Jordan Abbott, MD, who specializes in pediatric allergy and immunology, and Julie Lang, PhD, who specializes in microbiology and immunology.

The team is seeking to learn more about the immune system of people with single ventricle disease. They theorize that children with single ventricle disease are born with abnormal immune cells, so they plan to study immune cells in patients and in animal models to learn if cell abnormalities contribute to heart failure in single ventricle patients. They hope to determine if it’s possible to predict which single ventricle patients are at risk for complications and which medications may be most helpful to improve patient outcomes.

“We are finding that single ventricle patients are a distinct group and their differences may extend beyond their heart,” says Dr. Nakano. “On multiple levels, we are seeing differences in the single ventricle immune system that may contribute to the development of other complications. To truly improve outcomes in single ventricle patients, we need to study their unique biology to determine personalized and effective approaches.”