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Evaluation of a Novel Diagnostic Test for Calcium Release Deficiency Syndrome

Diagnose CRDS

Evaluation of a Novel Diagnostic Test for Calcium Release Deficiency Syndrome

Lead PI & Sponsor

Dr. Jason Roberts

Local PI

Dr. Habib Khan

Research Staff

Megan Smith

Objective

The primary objective of this study is to differentiate CRDS patients from CPVT patients, survivors of UCA, and healthy control subjects who don’t possess the RyR2 underactive gene variant. The investigators hypothesize that this can be achieved by assessing the response to ventricular and atrial pacing of the heart

Target Number of Patients

10

Currently Enrolled

0

Inclusion Criteria

  • For CRDS cases:
    a. Presence of an RyR2 variant confirmed to be loss-of-function on in vitro testing.
  • For CPVT cases:
    a. Clinical phenotype consistent with the Expert Consensus Statement. b. Presence of a confirmed or presumed pathogenic gain-of-function RyR2 variant.
  • For UCA cases:
    a. Cardiac arrest requiring cardioversion or defibrillation that remains unexplained following an ECG, echocardiogram, coronary assessment, cardiac MRI, exercise test, and sodium channel blocker provocation b. Underwent genetic testing where screening of RyR2 variant was included.
  • For SVT controls:
    a. Undergoing an electrophysiology study
    b. Normal baseline ECG

Exclusion Criteria

  • For CRDS cases:
    a. Unable to provide informed consent.
  • For CPVT cases: a. Unable to provide informed consent. b. Use of a QT prolonging medication, with the exception of flecainide, at the time of the burst pacing maneuvers
  • For UCA cases: a. unable to provide informed consent. b. Use of a QT prolonging medication at the time of burst pacing
    c. Use of a Class I and Class III antiarrhythmic drug at the time of burst pacing maneuvers
  • For SVT controls:
    a. Unable to provide informed consent
    b. Ventricular cardiomyopathy
    c. Ventricular pre-excitation
    d. Long QT syndrome
    e. Use of a QT prolonging medication at the time of their EP study
    f. Use of a class I or class III antiarrhythmic drug at the time of their EP study
    g. Known obstructive coronary artery disease

Millions of people suffer due to cardiac arrest every year and in many cases, the cause of the cardiac arrest is related to a disorder of the electrical activity of the heart. Calcium Release Deficiency Syndrome (CRDS) is a new electrical heart disorder that develops due to a genetic change in the RyR2 gene resulting in the low activity of RyR2 protein. Currently, CRDS needs genetic testing to be diagnosed where the assessment is confirmed in a science laboratory. Furthermore, most healthcare practitioners and patients lack access to a basic science laboratory. In order to identify a more convenient diagnostic test to clinically diagnose CRDS, we plan to observe and investigate the electrical response of the heart through an ECG after burst pacing the heart for a short period of time. We plan to comprehensively investigate to distinguish CRDS patients from Catecholaminergic Polymorphic Ventricular Tachycardia (CPVT) patients, and survivors of Unexplained Cardiac Arrest (UCA) patients who don’t have underactive RyR2 gene variant.