A Clinical Diagnostic Test for Calcium Release Deficiency Syndrome
Calcium Release Deficiency Syndrome (CRDS) is a newly discovered disease entity that is based on genetic change in the Ryanodine receptor gene type 2 (RyR2). The genetic variant or change in RyR2 that links with CRDS leads to loss of function of the protein (in contrast to the gain-of-function changes that are associated with Catecholaminergic Polymorphic Ventricular Tachycardia, a disease that seems to be much more frequently compared to CRDS).
CRDS was first identified in resuscitated individuals, those who are revived from unconsciousness or cardiac arrest. It required genetic testing and functional analysis of an eventual identified RyR2 variant, a process which takes several months. So far there was no diagnostic clinical test to identify such patients.
The current paper studied 10 patients with CRDS and compared the response to an electrical stimulation protocol, which was previously identified as a potent way to induce dangerous ventricular arrhythmias (like the arrhythmias that are recorded in the implantable cardioverter-defibrillators (ICD’s) of these patients when they suffer from recurrent events). On the ECG the focus was in particular on the first spontaneous complex that appeared shortly after a short ‘burst’, i.e. a train of electrical stimuli that slightly speeds up heart rate. The ST-segment of that heart beat is markedly different (much higher and much longer) in CRDS patients when compared with patients who were resuscitated successfully and not diagnosed with CRDS and compared with patients that were investigated because of benign supra-ventricular arrhythmias. The effect was consistently observed and it was therefore concluded that this test could well serve as a reliable test to diagnose CRDS patients.
This study is because of the small number of patients regarded as a preliminary or first study and more patients need to be studied before the test can be widely applied and become a standard test in the work-up of patients after an unexplained cardiac arrest.
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. A Clinical Diagnostic Test for Calcium Release Deficiency Syndrome.
JAMA 332, 204-213, 2024. PMID: 38900490
Prepared by Arthur Wilde and Lorraine McGlinchey