Objective
The primary objective of this study is to differentiate CRDS patients from CPVT patients, survivors of unexplained cardiac arrest, and healthy control subjects who do not 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.
Background
Millions of people suffer cardiac arrest every year, and in many cases the cause is related to a disorder of the electrical activity of the heart. Calcium Release Deficiency Syndrome (CRDS) is a newly described electrical heart disorder caused by a genetic change in the RyR2 gene resulting in low activity of the RyR2 protein. Currently, CRDS requires genetic testing confirmed in a science laboratory to be diagnosed, and most practitioners and patients lack access to such a laboratory. To identify a more convenient clinical diagnostic test, we plan to investigate the electrical response of the heart through an ECG after burst pacing the heart for a short period — distinguishing CRDS patients from CPVT patients and survivors of unexplained cardiac arrest who do not have the underactive RyR2 variant.
Study Outcomes
Primary
Secondary
Eligibility Criteria
The criteria below are a summary. Your study doctor will confirm whether this study is right for you.
Inclusion Criteria
- CRDS cases: presence of an RyR2 variant confirmed to be loss-of-function on in vitro testing
- CPVT cases: clinical phenotype consistent with the Expert Consensus Statement and a confirmed or presumed pathogenic gain-of-function RyR2 variant
- Unexplained cardiac arrest (UCA) cases: cardiac arrest requiring cardioversion or defibrillation that remains unexplained after standard workup, and genetic testing that included RyR2 screening
- SVT controls: undergoing an electrophysiology study with a normal baseline ECG
Exclusion Criteria
- Unable to provide informed consent (all groups)
- CPVT cases: use of a QT-prolonging medication (except flecainide) at the time of burst pacing maneuvers
- UCA cases: use of a QT-prolonging medication, or Class I or Class III antiarrhythmic drug, at the time of burst pacing
- SVT controls: ventricular cardiomyopathy, ventricular pre-excitation, long QT syndrome, use of QT-prolonging or Class I/III antiarrhythmic drugs, or known obstructive coronary artery disease
About taking part
If you would like to learn more about taking part in this study, please contact our research team using the details on this page. We can walk you through what participation involves and answer any questions.