New, Simple Clinical Test Detects Rare Life-Threatening Genetic Heart Condition

Calcium release deficiency syndrome (CRDS) is a life-threatening genetic arrhythmia that triggers dangerously rapid heartbeats, leading to severe complications like sudden cardiac arrest and death. Often, CRDS goes undetected by standard clinical tests, causing many cardiac arrests to be labeled as unexplained. This lack of detection prevents targeted care from being provided to survivors and at-risk family members. Now, a new, simple clinical test can identify CRDS by observing changes in electrocardiography (ECG) after a short period of rapid heartbeats followed by a pause, which can happen naturally or be induced by pacing the heart artificially.

In 2021, a research team from Hamilton Health Sciences (HHS, Ontario, Canada) confirmed the existence of this rare genetic syndrome. Until now, diagnosing CRDS has required specialized laboratory tests only available in research settings, which are not accessible to most doctors. This limitation has hampered the management and care of affected individuals and their families. In the latest research, an international team of researchers conducted a multi-centre case-control study involving 68 participants across 10 centers in seven countries, including HHS. This study grouped participants into four categories, including those diagnosed with CRDS and survivors of UCA. Additional research involving genetic mouse models has mirrored human findings and offered insights into the cellular mechanisms that produce the ECG signature indicative of CRDS.

This research is the initial phase in developing a diagnostic method for CRDS and gathering more data through the ongoing PHRI DIAGNOSE CRDS trial. This larger international effort aims to strengthen their findings. Currently in its recruitment phase, the DIAGNOSE CRDS trial plans to enroll 500 participants from 30 sites in 10 countries, including HHS. The impact of CRDS has led to numerous tragic events affecting families worldwide. The research team hopes that this simple pacing test will soon be integrated into routine diagnostic evaluations initially for UCAs, offering a new avenue for improving outcomes and preventing future tragedies.

“This novel and simple diagnostic method, which can be performed using an electrocardiogram in a broad range of clinical settings, is hopefully an important step towards improving our evaluation of initially unexplained cardiac arrest (UCA),” said HHS cardiac electrophysiologist Dr. Jason Roberts.

“This is an important discovery because there is an urgent need for a clinical diagnostic test for CRDS,” said Dr. Wayne Chen, a scientist and professor at the Libin Cardiovascular Institute and Hotchkiss Brain Institute at the University of Calgary’s Cumming School of Medicine. “This will allow us to identify individuals at risk, better understand the prevalence of CRDS and, hopefully, develop treatments for the condition.”

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Hamilton Health Sciences
University of Calgary