New screening test for people at risk of sudden cardiac arrest

The American Journal of Human Genetics (2022). DOI: 10.1016/j.ajhg.2022.05.002″ width=”800″ height=”530″/>
Graphic abstract. Credit: The American Journal of Human Genetics (2022). DOI: 10.1016/j.ajhg.2022.05.002

New research from the Victor Chang Cardiac Research Institute will allow families around the world to find out if they carry genetic mutations that cause sudden cardiac arrest, a disease that kills 9 out of 10 victims.

Institute researchers have developed a new electrical test that can screen for hundreds of genetic mutations to identify the exact mutations that are harmful to the hearts of people with inherited heart syndromes, which can lead to sudden death.

This breakthrough is a giant leap forward in the accuracy and precision of genetic testing that has profound implications not only for inherited heart conditions, but also for a wide range of neurological, muscle and kidney diseases.

Professor Jamie Vandenberg, who led the research published in two consecutive articles in the American Journal of Human Geneticssays that “It is mainly young people with otherwise healthy hearts who die from these inherited heart conditions and although this number is small, the consequences are long lasting.”

“When a person dies young, in their prime, it is so much more than the death of a single individual. The impact is felt on family and friends and it lasts forever.”

The other author, Dr Chai-Ann Ng, of the Victor Chang Cardiac Research Institute, says the ability to identify these dangerous mutations will prevent people from dying of sudden cardiac arrest and ensure that more people will be treated for this life-threatening disorder.

“If you can isolate the mutation and identify those at risk, there are lifestyle changes people can make, as well as taking beta-blockers or even using a defibrillator. Members of family can also get tested,” says Dr Ng.

“Genetic sequencing has revealed that we all contain a wide range of genetic variants, but we haven’t always been able to determine whether these variants are dangerous or not, only that they are different.”

“So when the genes are being tested right now, the clinical genetics lab can tell the patient, there’s a variant, but we don’t know if that increases your risk of cardiac arrest. It creates a tremendous amount of anxiety not only for the patient but also for the rest of the family who may also have inherited the mutation.We can now remove this uncertainty which is a great development.

Key statistics

  • Inherited arrhythmias are found in more than half of all initially unexplained cases of sudden cardiac death in young people.
  • Around 20,000 Australians suffer cardiac arrest outside of a hospital each year. Only 10% of people will survive an out-of-hospital cardiac arrest.

Professor Vandenberg’s team studied variants in the genes that code for ion channels, which are proteins that control the movement of electrical signals between cells. The majority of genetic disorders that lead to an increased risk of sudden cardiac arrest are caused by these mutations.

Main findings

  • In the first study, they developed a fast and accurate electrical test that assesses variants of an ion channel gene that causes an inherited cardiac arrhythmia called long QT syndrome type 2. They now classify all known variants of this gene to determine which are benign and dangerous and will upload the results to a giant genetic database that will be accessible to clinicians around the world.
  • The test they developed can easily be adapted to test for other ion channel genes, not just those associated with sudden cardiac arrest, but a wide range of other diseases spanning neurological, kidney and muscle disorders.
  • In the second paper, Prof. Vandenberg and his team collaborated with Dr. Kroncke of Vanderbilt University Medical Center to develop a new method based on high-throughput genome sequencing technology. This will allow them to assess the impact of each possible missense variant in KCNH2, which amounts to approximately 22,000 variants, within one to two years.


Professor Vandenberg says they “hope that within five years, as soon as someone has done their genetic test or sequenced their genome, they will know immediately if their variant is dangerous”.

“It’s amazing to think that we will be able to screen family members not just in Australia but all over the world and give them a diagnosis. Ultimately, this genetic database will reduce the number of cardiac arrests and deaths caused by genetic disorders.”

“In the short term, cardiology patients at risk of sudden death will benefit the most. But in the longer term, the research can be tailored to assess any of the approximately 400 different ion channel genes in the human genome that are associated with a wide range of neural disorders, muscle and kidney problems.”

Recommendations on genetic testing for inherited heart disease released today

More information:
Jamie I. Vandenberg, A Calibrated Functional Patch Clamp Assay to Improve the Interpretation of Clinical Variants in KCNH2-Related Long QT Syndrome, The American Journal of Human Genetics (2022). DOI: 10.1016/j.ajhg.2022.05.002

Chai-Ann Ng et al, Massively parallel assay accurately discriminates between functionally normal and abnormal variants in a KCNH2 hotspot domain, The American Journal of Human Genetics (2022). DOI: 10.1016/j.ajhg.2022.05.003

Provided by the Victor Chang Cardiac Research Institute

Quote: New screening test for those at risk of sudden cardiac arrest (June 9, 2022) Retrieved June 11, 2022 from

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