Precision Medicine Test Screens for Sudden Cardiac Arrest

New cardiac precision medicine genetic testing may be able to predict whose heart will suddenly stop before it actually happens

The practice of cardiovascular precision medicine is very much still evolving, but the prevalence of cardiovascular disease (CVD) in the US, and incidents of sudden cardiac arrest, make these areas ripe for ambitious research and development. Recent developments offer a glimpse into some of work in this broad precision medicine category.

First, a precision medicine test newly developed by Australian researchers may enable clinicians to quickly and accurately identify people who are at risk for sudden cardiac arrest, particularly stemming from inherited heart disorders.

“It’s primarily young people with otherwise healthy hearts that die from these inherited heart disorders and even though that number is small, the consequences are long-lasting,” stated lead researcher Jamie Vandenberg, MD, PhD, as part of the announcement from the Victor Chang Cardiac Research Institute.

Another researcher involved with the project is Chai-Ann Ng, PhD. Ng focuses on developing high-throughput methods to determine the risk for sudden cardiac arrest in patients with long QT syndrome, the heart rhythm disorder that can lead to sudden, uncontrollable, and dangerous arrhythmias, and sudden cardiac arrest.

Jamie Vandenberg, MD, PhD, and Chai-Ann Ng, PhD, of the Victor Chang Cardiac Research Institute in Australia announced their published research in the area of sudden cardiac arrest prevention. — Jamie Vandenberg, MD, PhD (left, above) and Chai-Ann Ng, PhD (right), are among the researchers at the Victor Chang Cardiac Research Institute in Australia, who have gained insights into dangerous variants in an ion gene channel of the heart that can lead to sudden cardiac arrest. (Photos: Victor Chang Cardiac Research Institute)

An interesting aspect of this new genetic screening test is that it targets ion channel gene variants to determine the harm in these variants, rather than their presence alone. Notable in this body of work are specialties in cardiac electrophysiology and high-throughput genome sequencing technology.

Detect Variants and Pinpoint Risk

The research explains that certain variations in the genes encoding an ion channel of the heart are responsible for sudden cardiac arrest. The researchers were able to identify which variants are cause for concern and which are not likely to lead to sudden cardiac arrest. Full details can be found in two back-to-back papers published in June in the American Journal of Human Genetics:

1. “A Calibrated Functional Patch-Clamp Assay to Enhance Clinical Variant Interpretation in KCNH2-Related Long QT Syndrome”

2. “A Massively Parallel Assay Accurately Discriminates Between Functionally Normal and Abnormal Variants in a Hotspot Domain of KCNH2”

The study investigated the utility of an automated patch-clamp assay for aiding clinical variant classification. According to the Institute, the findings will be used to develop a genetic database that will be accessible to other clinicians.

“Genetic sequencing has revealed that all of us contain a vast array of genetic variants, but we have not always been able to pinpoint if these variants are dangerous or not, only that they are different,” explained Ng in the announcement.

“So when genes are currently tested, the clinical genetics lab may tell the patient, ‘There’s a variant, but we don’t know whether it raises your risk of cardiac arrest,’” Ng continued. “That creates a huge amount of anxiety not just 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 big development.

“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,” Ng said.

Test Development Adds to Previous Research

This recent development builds on previous precision medicine cardiology research from the Victor Chang Cardiac Research Institute. In February 2022, the Institute in collaboration with the Icahn School of Medicine at New York’s Mount Sinai and other sites, identified which genes were likely to cause coronary heart disease.

According to researchers, whose work was published in the journal Circulation: Genomic and Precision Medicine, there were three key breakthroughs that helped make this a vital advance in precision cardiac medicine. These included:

Identifying 162 genes that are likely to cause coronary heart disease;
Identifying where in the body these genes had an effect; and
Ranking these genes in order of priority for likelihood of causing heart disease.

Because of this research, clinicians may be able to use precision medicine testing to accurately predict the risk of a heart attack.

“In the short term, it’s cardiology patients who are at risk of sudden death that will benefit most,” said Vandenberg, whose bio states that he is a member of the ion channel working group advising the Food and Drug Administration on the development of better assays to screen for cardiotoxicity of all new drugs. “But in the longer term, the research can be adapted to assess any of the approximate 400 different ion channel genes in the human genome which are associated with a wide range of neural disorders, muscle and kidney problems.”

Cardiac Precision Medicine: Where to Start

As healthcare leaders know, improving the overall care and economics of coronary, cardiac, and cardiovascular conditions is one of the great challenges at the forefront of medicine and medical technology.

“Despite a clear path forward toward mainstream application of precision medicine, there continues to be debate about whether a precision medicine approach will have a global impact on cardiovascular disease prevention and treatment or will only serve a small group of patients and be relegated to a highly selected niche role,” states an American Heart Association Circulation Research open access article from 2018, titled “Emerging Role of Precision Medicine in Cardiovascular Disease.”

Because implementing precision medicine in the practice of cardiovascular healthcare can vary widely, starting with a niche area where it is reasonable to expect cost savings and improved outcomes in a particular population may present immediate opportunities for hospitals and health systems.

Regardless, effective intervention tools that can predict and identify risk of cardiac events before they occur will enable healthcare leaders to provide value-based care that focuses on prevention instead of treatment.

—Caleb Williams