Evaluation of A Clinical Diagnostic Test for CRDS
Evaluation of a Clinical Diagnostic Test for Calcium Release Deficiency Syndrome: The DIAGNOSE CRDS Study
Population Health Research Institute
400 participants
Feb 2, 2023
INTERVENTIONAL
Conditions
Summary
Calcium Release Deficiency Syndrome (CRDS) is a novel inherited arrhythmia syndrome secondary to RyR2 loss-of-function that confers a risk of sudden cardiac death. Diagnosis of CRDS presently requires cellular-based in vitro confirmation that an RyR2 variant causes loss-of-function. We hypothesize that CRDS can be diagnosed clinically through evaluation of the repolarization response to brief tachycardia, mediated by cardiac pacing, and a subsequent pause.
Eligibility
Inclusion Criteria7
- Cohort 1: Calcium Release Deficiency Syndrome (CRDS) Cases
- Presence of an RyR2 variant confirmed to be loss-of-function on in vitro testing
- 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
- Cardiac arrest requiring cardioversion or defibrillation that remains unexplained following an ECG, echocardiogram, coronary assessment, cardiac MRI, and exercise treadmill test
- Undergone genetic testing that includes screening of RyR2*
- Undergoing an invasive electrophysiology study
Exclusion Criteria16
- Unable to provide informed consent
- Cohort 2: Catecholaminergic Polymorphic Ventricular Tachycardia (CPVT) Cases
- Unable to provide informed consent
- Use of a QT prolonging medication, aside from flecainide, at the time of the burst pacing maneuvers
- Cohort 3: Survivors of Unexplained Cardiac Arrest (UCA)
- Unable to provide informed consent
- Use of a QT prolonging medication at the time of the burst pacing maneuvers
- Among survivors of UCA that possess a rare RyR2 variant in the absence of a CPVT phenotype, in vitro functional testing will be performed in order to confirm it is not loss- or gain-of-function (and will be arranged through the laboratory of Dr. Wayne Chen at the University of Calgary).
- Cohort 4: SVT controls
- 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
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Interventions
1. Ventricular 10 beat burst at 500ms (120bpm) 2. Ventricular 10 beat burst at 400ms (150bpm) 3. Atrial 10 beat burst at 500ms (120bpm) 4. Atrial 10 beat burst at 400ms (150bpm).
Locations(18)
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NCT06188689