Researcher develops blood test for diagnosing congenital heart defect

The aortic valve is critical as it regulates blood flow from the heart to the aorta, the major vessel that delivers oxygen-rich blood to the body. Normally, the aortic valve has three leaflets, but about two per cent of the population has a bicuspid aortic valve (BAV), meaning there are just two leaflets, making it the most common congenital heart defect.

While individuals can go their whole life not knowing they have a BAV, the condition is associated with a risk of aneurysm or rupture, which can be fatal. University of Calgary researchers have discovered that the altered flow caused by the bicuspid valve creates stress on the aortic wall, sometimes causing it to dissect, bulge or rupture.

To prevent a possibly fatal rupture, cardiac surgeons may recommend aortic valve replacement. But knowing who should receive surgery and when can be a tough call.

“Right now, there isn’t really a simple diagnostic blood test for aortopathy (aortic disease) or a clear picture of who would benefit from surgery,” says Dr. Steven Greenway, MD, a clinician-researcher in the departments of Cardiac Sciences, Paediatrics and Biochemistry and Molecular Biology at the Cumming School of Medicine (CSM).

Finding the answers to this, and other important clinical questions, is Greenway’s motivation for participating in a Calgary-based research collaboration looking at using blood-based biomarkers, coupled with advanced cardiac imaging, to identify individuals who would benefit most from valve replacement surgery.

Greenway’s translational research focuses on solving the problems he sees in his practice as a paediatric cardiologist. He specializes in using gene sequencing, genomics and epigenomics, which combines the study of genetic and environmental factors, to develop diagnostic tests and treatments for complex conditions like BAV and other heart conditions.

In collaboration with Dr. Paul Fedak, MD, PhD, a cardiac surgeon, researcher at the CSM, and director of the Libin Cardiovascular Institute, using samples collected from patients with BAV, Greenway and his master’s student Ashna Maredia found aorta-specific DNA fragments in the blood of individuals with the condition. Levels of these fragments reflected altered flow and wall stress in the aorta as determined by cardiac magnetic resonance imaging (MRI). These fragments are potential biomarkers, signalling the condition for diagnostic purposes.

Greenway and Fedak received an Alberta Innovates grant to develop a blood test based on these biomarkers to help identify individuals with BAV who would benefit most from surgery. A positive blood test would signal the need for comprehensive screening using cardiac MRI. In conjunction, these two methods could serve as powerful clinical tools in determining the best treatment options for patients.

Greenway, who has been working in Calgary since 2012, enjoys the collaborative opportunities available within the Libin Cardiovascular Institute, of which he is a member.

“When clinicians and researchers with different specialties work together, that is where the big ideas happen and novel discoveries are made,” he says.