New electrical test to screen people at risk of sudden cardiac arrest

New research from the Victor Chang Cardiac Research Institute will enable families around the world to discover if they carry genetic mutations that cause sudden cardiac arrest – a condition that kills nine out of 10 victims.

Researchers at the Institute have developed a new electrical test that can screen hundreds of gene mutations to detect the exact mutations that harm the hearts of people suffering from hereditary heart disease, which can cause sudden death.

The breakthrough is a giant step forward in the accuracy and precision of genetic testing that has profound implications not only for hereditary heart disease, but also for a wide variety of neurological, musculoskeletal and kidney diseases.

Professor Jamie Vandenberg, who led the research published in two back-to-back papers in the American Journal of Human Geneticssays: “It is mainly young people with otherwise healthy hearts who die from these hereditary heart conditions and while that number is small, the consequences are long-lasting

“When someone dies young, in the prime of life, it’s much more than just the death of one person. The impact is felt on the family and their friends and it lasts forever.

Fellow author Dr. Chai-Ann Ng, of the Victor Chang Cardiac Research Institute, says being able to identify these dangerous mutations will prevent people from dying of sudden cardiac arrest and ensure more people receive treatment for this life-threatening condition.

If you can isolate the mutation and identify the groups at risk, there are lifestyle changes people can make, as well as taking beta blockers or even using a defibrillator. Family members can also be tested.

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

So when genes are currently being tested, the clinical genetics lab can tell the patient: There is a variant, but we don’t know if it increases your risk of cardiac arrest. That creates an enormous amount of fear, not only for the patient, but also for the rest of the family who may also have inherited the mutation. We can now remove that uncertainty, which is a major development.”

dr. Chai-Ann Ng, Victor Chang Cardiac Research Institute

Key Statistics

• Hereditary arrhythmias account for more than half of all initially unexplained cases of sudden cardiac death in young people.
• Every year about 20,000 Australians go into cardiac arrest outside a hospital. Only 10% of people survive a cardiac arrest outside the hospital.

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

Key findings

• In the first study, they developed a rapid and accurate electrical test that assesses variants in an ion channel gene that causes an inherited heart rhythm disorder called Long QT syndrome type 2. They now classify all known variants in this gene to determine which are benign and which are dangerous. and will upload the findings to a massive genetic database that will be accessible to clinicians around the world.
• The test they developed could easily be adapted to test other ion channel genes – not just genes linked to sudden cardiac arrest, but a wide variety of other diseases that include neurological, kidney and muscle disorders.
• In the second paper, Professor 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 allows them to estimate the impact of each possible missense variant in KCNH2 within one to two years, which amounts to approximately 22,000 variants.

Influence

Professor Vandenberg says: “We hope that within five years, once someone has tested their genes or sequenced their genomes, they will immediately discover whether their variant is dangerous.

“It’s incredible to think that we can screen and diagnose family members not just across Australia but anywhere in the world. Ultimately, this genetic database will reduce the number of cardiac arrests and deaths from genetic disorders.

“In the short term, cardiology patients at risk of sudden death will benefit the most. But in the longer term, the study could be adapted to assess each 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.”