Jonathan B. Wagner, DO

Matson Family Endowed Professorship in Cardiac Research; Division Director, Clinical Pharmacology, Toxicology & Therapeutic Innovation; Co-Program Director Pediatric Clinical Pharmacology Fellowship Program; Professor of Pediatrics, University of Missouri-Kansas City School of Medicine

Full Biography

Jonathan Wagner, DO, Clinical Pharmacology, Toxicology & Therapeutic Innovation and the Ward Family Heart Center, received $150,000 in funding for his study “IMProving Drug dosing and Outcomes for single Ventricle patients with Fontan Associated Liver Disease (IMPROVE-FALD).”

The funding came from a Maternal and Pediatric Precision in Therapeutics (MPRINT) Knowledge and Research coordination (KRCC) P30 Pilot award via Indiana University from the National Institute of Health’s Eunice Kennedy Shriver National Institute of Child Health and Human Development.

“With more children that had heart surgery living, we are seeing different blood flows from the surgery leading to problems outside of the heart as they get older,” said Dr. Wagner.

This study focuses on children who have had the Fontan procedure. These are children with severe heart disease with only one functional ventricle. The Fontan procedure helps increase the oxygen in the blood and helps the work of the heart by taking a blood vessel from the bottom part of the body that flows back to the heart and moves it to the blood vessels going to the lungs.

This new blood flow system does not have a pump chamber to push blood forward, instead relying on blood to passively drain to the lungs.

Over time, this system of slow, passive blood flow leads to more pressure in the blood vessels coming back to the heart and lungs. The liver, which is close to the heart and lungs, is one of the first areas affected. This slow-moving blood flow in the liver causes the liver structure to change. Liver changes like fullness and scaring are called Fontan-Associated Liver Disease (FALD).

“Although we are better at checking for FALD through getting tests that can show us pictures of the liver, we do not know how different grades of FALD based on these tests relate to how well the liver is working,” explains Dr. Wagner. “We are unsure if FALD grades tell us how well the liver can process chemicals and drugs, which we know can be affected when adults have liver problems for a long time.”

There is a known gradual decline in survival following Fontan surgery and the challenges related to and limited availability of liver or heart transplantation, so effective medical management is important.

This study will look at liver fullness and scaring using liver Magnetic Resonance Imaging (MRI) and compare it to how well a drug is broken down and moved by the liver after a dose is given. If the child’s liver health predicts differences in the amount of drug in the blood and this, in turn, predicts how well the drug works, doctors will then be able to “personalize” dosing for children and adolescents with the Fontan surgery.

There are two major goals for the results of this study: That it will make drug treatment better and safer for these patients and that it will help to know at what amount of liver fullness and scaring that liver function is impaired in order to help the medical team improve decisions about medications, further heart surgeries, or heart transplant.

Sherwin Chan, MD, PhD, Radiology, and Emily Cramer, PhD, Health Services & Outcomes Research, will service as co-investigators.

The contents are those of the investigator and do not necessarily represent the official views of, nor an endorsement, by NIH, or the U.S. Government.