Provocation with brief tachycardia and a subsequent pause resulted in a significantly higher median change in T-wave amplitude in patients with calcium release deficiency syndrome compared to controls, demonstrating 100% discrimination.
Case-Control (n=68)
Single-blind
Yes
Does provocation with brief tachycardia and a subsequent pause produce a unique repolarization response on an electrocardiogram to diagnose Calcium Release Deficiency Syndrome (CRDS)?
A brief tachycardia followed by a pause elicits a unique, highly discriminative repolarization response (increased T-wave amplitude) on ECG that can accurately diagnose Calcium Release Deficiency Syndrome.
p-value: p=<0.001
Importance: Sudden death and cardiac arrest frequently occur without explanation, even after a thorough clinical evaluation. Calcium release deficiency syndrome (CRDS), a life-threatening genetic arrhythmia syndrome, is undetectable with standard testing and leads to unexplained cardiac arrest. Objective: To explore the cardiac repolarization response on an electrocardiogram after brief tachycardia and a pause as a clinical diagnostic test for CRDS. Design, Setting, and Participants: An international, multicenter, case-control study including individual cases of CRDS, 3 patient control groups (individuals with suspected supraventricular tachycardia; survivors of unexplained cardiac arrest UCA; and individuals with genotype-positive catecholaminergic polymorphic ventricular tachycardia CPVT), and genetic mouse models (CRDS, wild type, and CPVT were used to define the cellular mechanism) conducted at 10 centers in 7 countries. Patient tracings were recorded between June 2005 and December 2023, and the analyses were performed from April 2023 to December 2023. Intervention: Brief tachycardia and a subsequent pause (either spontaneous or mediated through cardiac pacing). Main Outcomes and Measures: Change in QT interval and change in T-wave amplitude (defined as the difference between their absolute values on the postpause sinus beat and the last beat prior to tachycardia). Results: Among 10 case patients with CRDS, 45 control patients with suspected supraventricular tachycardia, 10 control patients who experienced UCA, and 3 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 (P < .001). 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 (P = .002), 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 release of calcium from the sarcoplasmic reticulum. Conclusions and Relevance: There is a unique repolarization response on an electrocardiogram after provocation with brief tachycardia and a subsequent pause in CRDS cases and mouse models, which is absent from the controls. If these findings are confirmed in larger studies, this easy to perform maneuver may serve as an effective clinical diagnostic test for CRDS and become an important part of the evaluation of cardiac arrest.
Ni et al. (Thu,) conducted a case-control in Calcium Release Deficiency Syndrome (CRDS) (n=68). Brief tachycardia and a subsequent pause (provocation maneuver) vs. Control patients (SVT, UCA, CPVT) was evaluated on Change in T-wave amplitude on the postpause sinus beat (p=<0.001). Provocation with brief tachycardia and a subsequent pause resulted in a significantly higher median change in T-wave amplitude in patients with calcium release deficiency syndrome compared to controls, demonstrating 100% discrimination.