Understanding a silent danger
No way to predict sudden heart failure in a healthy adolescent
A healthy teenager suddenly collapses during soccer practice and dies. After his death, physicians find he was harboring a silent killer known as hypertrophic cardiomyopathy, a condition in which the heart muscle becomes thickened, making it harder to pump blood out of the heart.
The condition generally has no symptoms, but it is the most common killer of adolescents who are otherwise healthy and is the leading reason for heart transplants in children.
Despite its prevalence, very little is known about the genetic and molecular makeup or the electrical phenotypes of the hearts of children with hypertrophic cardiomyopathy. New research funded by the Children’s Discovery Institute may change that.
Jeanne M. Nerbonne, PhD, the Alumni Endowed Professor of Molecular Biology and Pharmacology in Developmental Biology, and her colleagues received a large initiative grant from the Institute to develop the Translational Cardiovascular Tissue Core, a centralized system for acquiring, banking, annotating with clinical data, and distributing tissue from diseased hearts. It is directed by Kathryn A. Yamada, PhD, professor of medicine in the Cardiovascular Division.
“As individuals develop heart failure,” says Nerbonne, “we do not know how to predict who is going to have the fatal sudden death incident. It has become increasingly clear that detailed electrophysiological and molecular analyses of diseased and non-diseased human hearts are urgently needed to advance the field.”
Nerbonne, professor of medicine, and her team take tissue samples from the diseased hearts of children at the time they get a ventricular-assist device, which helps the heart pump blood and is often used as a bridge to a heart transplant. Investigators then perform various studies on these tissues, looking at the proteins, RNA, cellular and whole tissue physiology, as well as bank tissue for genetic and epigenetic analyses. They also collect diseased hearts at the time of transplant and perform similar studies, comparing what they find with non-diseased heart tissue.
Notably, the banked tissue and associated data will be available to all Washington University investigators for further types of analysis.
“As the science moves forward,” Nerbonne says, “other researchers will be able to take a different look at the data for new discoveries.”