A Clinical Diagnostic Test for Calcium Release Deficiency Syndrome.

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.

Local VA index for the differential diagnosis of supraventricular tachycardia.

BACKGROUND: Differentiating between atypical atrioventricular nodal reentrant tachycardia (AVNRT) and orthodromic reciprocating tachycardia utilizing a septal accessory pathway is a complex challenge. OBJECTIVE: The purpose of this study was to describe the "local VA index," a straightforward method based on signals from the coronary sinus catheter, to distinguish between these arrhythmias during tachycardia and entrainment. The ventriculoatrial (VA) interval on the coronary sinus catheter is measured during tachycardia and entrainment, at the site of earliest atrial activity. The difference between these 2 situations defines the "local VA index." We also propose a mechanism to clarify the limitations of historical pacing maneuvers, such as postpacing interval minus tachycardia cycle length (PPI-TCL) and stimulus-atrial interval minus ventriculoatrial interval (SA-VA), by examining nodal decrement and intraventricular conduction delay. METHODS: In a retrospective study of 75 patients referred for supraventricular tachycardia evaluation, 37 were diagnosed with atrioventricular reentrant tachycardia (AVRT) with orthodromic reciprocating tachycardia, and 38 with AVNRT (27 typical, 11 atypical). RESULTS: In comparison to AVRT patients, AVNRT patients exhibited longer PPI-TCL (176 ± 47 ms vs 113 ± 42 ms; P <.01) and SA-VA (138 ± 47 ms vs 64 ± 28 ms; P <.01). The AVRT group had mean local VA index of -1 ± 13 ms, whereas the AVNRT group had a significantly longer index of 91 ± 46 ms (P <.01). An optimal threshold for differentiation was a local VA index of 40 ms. Importantly, there was no significant correlation between pacing cycle length and nodal decrement as well as intraventricular delay related to pathway location. This interindividual variability might explain misleading interpretations of PPI-TCL and SA-VA. CONCLUSION: This novel approach is advantageous because of its simplicity and effectiveness, requiring only 2 diagnostic catheters. A local VA interval difference <40 ms provides a clear distinction for AVRT.