World’s first individual gene mutation test

… for predicting risk of sudden cardiac death.

Scientists at the Victor Chang Cardiac Research Institute have developed a world-first individualised risk prediction tool for people suffering from a type of heart arrhythmia that can cause sudden cardiac arrest.

This is the first time a gene mutation-specific test has been applied to predict the severity of heart disease.

The discovery was made in conjunction with colleagues at the Vanderbilt University Medical Centre and could also benefit patients suffering from other heart arrhythmias and neurological conditions.

Lead author Professor Jamie Vandenberg, Deputy Director of the Victor Chang Cardiac Research Institute, says the findings published in Circulation would enable patients with one of the most common inherited heart diseases – Long QT syndrome – to discover how severe their condition was.

Professor Vandenberg says: “Genetic testing for inherited heart diseases has been transformative, but there have been limitations in what it can tell you. It might reveal you have the disease, but there has been no way of using this genetic information to determine how high your risk is for suffering a sudden cardiac arrest.

“This will provide patients and their families with answers and better enable clinicians to tailor treatment appropriately.”

Long QT Syndrome is a heart rhythm disorder that can cause sudden cardiac death and generally affects people who are otherwise fit and healthy. Around one in 2000 Australians will have this condition.

Nine out of 10 people who have a sudden cardiac arrest outside of hospital will survive, making this discovery even more significant.

The researchers investigated 533 genetic variants or mutations associated with Long QT syndrome from 1458 patients. The mutations affect the function of ion channel gene variants.

They analysed every mutation and its function using a high-speed electrical test, a high-throughput automated patch clamp assay.

They revealed which genetic mutations were the most dangerous by comparing these findings against traditional testing methods and using patient records.

They discovered that some genetic mutations reduced the function of the ion channel by up to 90 percent, resulting in a 13.3-fold greater risk of major cardiac events (arrhythmia, sudden death). A 75 percent reduction in function was associated with an 8.6-fold greater risk of major cardiac events.

Fellow author Dr Chai-Ann Ng of the Victor Chang Cardiac Research Institute says: “We have shown that not every diagnosis of Long QT is equal, and the risk of having a sudden cardiac arrest can vary dramatically depending on the exact genetic mutation.

“Our findings will make a huge difference in how these high-risk patients are cared for in the future. We are also actively working on adapting this test to patients affected by other heart arrhythmias and neurological conditions.”

Journal: Circulation
DOI: 10.1161/CIRCULATIONAHA.124.069828
Method of Research: Data/statistical analysis
Subject of Research: Cells
Article Title: Assays of Variant Effect and Automated Patch Clamping Improve KCNH2-LQTS Variant Classification and Cardiac Event Risk Stratification
Article Publication Date: 25-Sep-2024

Media Contact

Julia Timms
Victor Chang Cardiac Research Institute
j.timms@victorchang.edu.au
Cell: +61457-517-355

www.victorchang.edu.au