Study Unveils Novel ECG Marker for CRDS: Potential Breakthrough in Cardiac Arrest Diagnosis

The preliminary findings published in the Journal of the American Medical Association (JAMA) suggest that the repolarization response on an electrocardiogram (ECG) following brief tachycardia and subsequent pause shows promise as an effective diagnostic indicator for CRDS.

"Considering the prevalence of unexplained cardiac arrest, if confirmed in larger studies, this readily available procedure could offer clinically actionable insights," the researchers wrote.

The multicenter, international, case-control study showed that a provoked measure of T-wave amplitude on an ECG ascertained CRDS cases with high accuracy. The genetic mouse models mirrored the human findings and indicated that an excessively large systolic calcium release from the sarcoplasmic reticulum was likely the cause.

CRDS, a genetic disorder characterized by impaired calcium release from the sarcoplasmic reticulum in muscle cells, presents with diverse symptoms ranging from muscle weakness and fatigue to potentially life-threatening cardiac arrhythmias. Until now, diagnosing CRDS has been challenging due to its rarity and complex clinical presentation, often leading to delays in treatment and management.

Against the above background, Mingke Ni, University of Calgary, Calgary, Alberta, Canada, and colleagues aimed to explore the cardiac repolarization response on an ECG after brief tachycardia and a pause as a clinical diagnostic test for CRDS.

An international, multicenter, case-control study conducted across 10 centers in 7 countries included cases of CRDS and three control groups: individuals with suspected supraventricular tachycardia, survivors of unexplained cardiac arrest (UCA), and individuals with genotype-positive catecholaminergic polymorphic ventricular tachycardia (CPVT). The study also utilized genetic mouse models (CRDS, wild type, and CPVT) to elucidate the cellular mechanism underlying the condition. Patient tracings were recorded between 2005 and 2023.

The main outcome was a change in QT interval and a change in T-wave amplitude (defined as the difference between their absolute values on the post-pause sinus beat and the last beat before tachycardia).

The following were the key findings of the study:

• Among ten case patients with CRDS, 45 control patients with suspected supraventricular tachycardia, ten control patients who experienced UCA, and three control patients with genotype-positive CPVT, the median change in T-wave amplitude on the postpause sinus beat (after brief ventricular tachycardia at ≥150 beats/min) was higher in patients with CRDS.
• The smallest change in T-wave amplitude was 0.250 mV for a CRDS case patient compared with the largest change in T-wave amplitude of 0.160 mV for a control patient, indicating 100% discrimination.
• Although the median change in QT interval was longer in CRDS cases, an overlap between the cases and controls was present.
• The genetic mouse models recapitulated the findings observed in humans and suggested the repolarization response was secondary to a pathologically large systolic calcium release from the sarcoplasmic reticulum.

The findings revealed a unique repolarization response on an ECG after provocation with brief tachycardia and a subsequent pause in CRDS cases and mouse models, which is absent from the controls.

"These findings, if confirmed in larger studies, this easy-to-perform maneuver could be an effective clinical diagnostic test for CRDS and become an important part of the cardiac arrest evaluation," the researchers concluded.

Reference:

Ni M, Dadon Z, Ormerod JOM, et al. A Clinical Diagnostic Test for Calcium Release Deficiency Syndrome. JAMA. Published online June 20, 2024. doi:10.1001/jama.2024.8599