UCalgary researcher co-leads international team that develops simple test for fatal genetic heart condition

A team of international researchers has revealed a new, simple clinical test to detect Calcium Release Deficiency Syndrome (CRDS), a life-threatening genetic arrhythmia that causes dangerously fast heartbeats and can lead to sudden cardiac arrest and death.

The research was co-led by Dr. Wayne Chen, PhD, a professor and scientist at the Cumming School of Medicine, and Dr. Jason Roberts, MD, a cardiac electrophysiologist and scientist at the Population Health Research Institute (PHRI), a joint institute of McMaster University and Hamilton Health Sciences. 

The new diagnostic method monitors for changes in electrocardiography (ECG) after a brief period of a fast heartbeat followed by a pause, which can occur naturally or be induced by artificially pacing the heart and can be performed using an electrocardiogram in a broad range of clinical settings.

Chen led an international team that first identified CRDS in 2021, solving a 20-year mystery about the fatal heart flaw, which is linked to sudden cardiac arrest. But CRDS remained undetectable with standard clinical tests, often resulting in the cardiac arrests being labeled as unexplained. That concern has now been resolved.

“This is an important discovery because there is an urgent need for a clinical diagnostic test for CRDS,” says Chen. “This will allow us to identify individuals at risk, better understand the prevalence of CRDS and, hopefully, develop treatments for the condition.”

The multi-centre case-control study involved 68 study participants from 10 centres in seven countries. The participants were from four categories of heart conditions, including CRDS patients. Findings are published in JAMA.

Accompanying studies from Chen’s lab revealed findings in genetic mouse models that mirrored those observed in humans. The mouse studies also provided insight into the underlying cellular mechanism responsible for this apparent ECG signature of CRDS.

"CRDS has been linked to many tragic incidents and heartbreaking stories affecting families. There have been numerous cases where patients experienced fainting episodes, but their tests showed no issues, which led doctors to believe the fainting was not due to a dangerous heart condition,” says Roberts. “A portion of these individuals, often young and otherwise healthy, subsequently suffered sudden cardiac arrests, and some did not survive.” 

The study marks the initial stage of Chen and Roberts’ efforts to further explore a diagnostic approach for CRDS and collecting additional data as part the ongoing PHRI DIAGNOSE CRDS trial. This trial represents a broader, international initiative aimed at strengthening their conclusions. Currently in the recruitment phase, DIAGNOSE CRDS aims to enroll 500 participants from 30 sites across 10 countries.

“We hope this test will help many families worldwide who have faced unexplained cardiac incidents or lost loved ones to them,” says Roberts.

The team anticipates this simple pacing test will be incorporated into the routine diagnostic tests for initially unexplained cardiac arrest, providing hope for better outcomes and prevention of future tragedies.

Funding for this project was supported by the Canadian Institutes of Health Research and the Heart and Stroke Foundation. The team also received support from the Genomics of Unexplained Cardiac Arrest (GenUCA) project, which is funded by the British Heart Foundation, the German Center for Cardiovascular Research and the Dutch Heart Foundation.