A Clinical Diagnostic Test for Calcium Release Deficiency Syndrome.
Ni M., Dadon Z., Ormerod JOM., Saenen J., Hoeksema WF., Antiperovitch P., Tadros R., Christiansen MK., Steinberg C., Arnaud M., Tian S., Sun B., Estillore JP., Wang R., Khan HR., Roston TM., Mazzanti A., Giudicessi JR., Siontis KC., Alak A., Acosta JG., Divakara Menon SM., Tan NS., van der Werf C., Nazer B., Vivekanantham H., Pandya T., Cunningham J., Gula LJ., Wong JA., Amit G., Scheinman MM., Krahn AD., Ackerman MJ., Priori SG., Gollob MH., Healey JS., Sacher F., Nof E., Glikson M., Wilde AAM., Watkins H., Jensen HK., Postema PG., Belhassen B., Chen SRW., Roberts JD.
ImportanceSudden 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.ObjectiveTo explore the cardiac repolarization response on an electrocardiogram after brief tachycardia and a pause as a clinical diagnostic test for CRDS.Design, setting, and participantsAn 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.InterventionBrief tachycardia and a subsequent pause (either spontaneous or mediated through cardiac pacing).Main outcomes and measuresChange 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).ResultsAmong 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 Conclusions and relevanceThere 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.