Diagnose CRDS

Evaluation of a novel diagnostic test for Calcium Release Deficiency Syndrome (CRDS)

Diagnosis of calcium release deficiency syndrome (CRDS) currently requires laboratory-based in vitro evaluation of the pathogenic RyR2 loss-of-function variant. Given the lack of availability for this testing, a clinically-based diagnostic test must be developed to readily enable the diagnosis of CRDS. The purpose of this study is to investigate the response to either an atrial or ventricular pacing train as a diagnostic test for CRDS.

Enrolment Criteria

Inclusion

Prospective CRDS cases:
• Presence of an RyR2 variant confirmed to be loss-of-function on in vitro testing
CPVT cases:
• Satisfy a clinical phenotype consistent with the Expert Consensus Statement
• Presence of a confirmed or presumed pathogenic gain-of-function RyR2 variant OR homozygous or compound heterozygous for likely pathogenic/pathogenic CASQ2 variants
Survivors of UCA variant:
• Cardiac arrest requiring cardioversion or defibrillation that remains unexplained following an ECG, echocardiogram, coronary assessment, cardiac MRI, exercise treadmill test, and sodium channel blocker provocation
• Undergone genetic testing that includes screening of RyR2
SVT control participants:
• Undergoing an invasive electrophysiology study
• Normal baseline ECG
Exclusion

Prospective CRDS cases:
• Unable to provide informed consent (unless the maneuvers had previously been performed and the patient is no longer accessible for consent)
CPVT cases:
• Unable to provide informed consent (unless the maneuvers had previously been performed and the patient is no longer accessible for consent)
• Use of a QT-prolonging medication, aside from flecainide, at the time of the burst pacing maneuvers
Survivors of UCA variant:
• Unable to provide informed consent (unless the maneuvers had previously been performed and the patient is no longer accessible for consent)
• Use of a QT-prolonging medication at the time of the burst pacing maneuvers
SVT control participants:
• Ventricular cardiomyopathy
• Ventricular pre-excitation
• Long QT syndrome
• Use of a QT-prolonging medication at the time of the EP study
• Use of a Class I or Class III anti-arrhythmic drug at the time of the EP study
• Known obstructive coronary artery disease (existing coronary stenosis >50%)
• Unable to provide informed consent (unless the maneuvers had previously been performed and the patient is no longer accessible for consent)