Evaluation of A Clinical Diagnostic Test for CRDS

Launched by POPULATION HEALTH RESEARCH INSTITUTE · Dec 18, 2023

Keywords

ClinConnect Summary

This clinical trial is studying a new way to diagnose Calcium Release Deficiency Syndrome (CRDS), a rare heart condition that can lead to serious heart problems, including sudden cardiac death. Currently, diagnosing CRDS requires complex lab testing that confirms a specific genetic change in a protein called RyR2. The researchers believe they can simplify diagnosis by observing how the heart responds to a brief rapid heartbeat, which is induced by a pacing device, followed by a pause.

The trial is looking for participants from different groups: people already diagnosed with CRDS who have a confirmed RyR2 genetic change, individuals with another heart condition called Catecholaminergic Polymorphic Ventricular Tachycardia (CPVT), survivors of unexplained cardiac arrest, and control participants undergoing a specific heart study. To be eligible, participants need to provide informed consent and meet specific criteria, such as having certain genetic tests completed. Those who join can expect to undergo heart pacing tests to help researchers understand the effectiveness of this new diagnostic approach. This trial is important because it aims to make diagnosing CRDS easier and faster, potentially saving lives.

Gender

ALL

Eligibility criteria

• • Cohort 1: Calcium Release Deficiency Syndrome (CRDS) Cases
• Inclusion criteria:
• • • Presence of an RyR2 variant confirmed to be loss-of-function on in vitro testing
• Exclusion criteria:
• • • Unable to provide informed consent
• • Cohort 2: Catecholaminergic Polymorphic Ventricular Tachycardia (CPVT) Cases
• Inclusion criteria:
• • 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
• Exclusion criteria:
• • 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)
• Inclusion criteria:
• • 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\*
• Exclusion criteria:
• • 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
• Inclusion criteria:
• • • Undergoing an invasive electrophysiology study
• Exclusion criteria:
• • 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