Clinical Trials

Prospective CRDS cases meeting the following inclusion and exclusion criteria will be eligible:

Inclusion Criteria:

•  Presence of an RyR2 variant confirmed to be loss-of-function on in vitro testing.

Exclusion Criteria:

•  Unable to provide informed consent (unless the maneuvers had previously been performed and the patient is no longer accessible for consent).

CPVT cases meeting the following inclusion and exclusion criteria will be eligible:

Inclusion Criteria:

• Satisfy a clinical phenotype consistent with the Expert Consensus Statement10.

• 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 (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 wil be eligible provided that they meet the following inclusionand exclusion criteria:

Inclusion Criteria:

• 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.

Exclusion Criteria:

• 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.
• Among survivors of UCA that possess a rare RyR2 variant in the absence of a CPVT. phenotype, in vitro functional testing will need to be performed in order to confirm it is not loss-of-function (and will be arranged through the laboratory of our collaborator, Dr.

SVT control participants meeting the following inclusion and exclusion criteria will be eligible:

Inclusion Criteria:

• Undergoing an invasive electrophysiology study.
• Normal baseline ECG.

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 (unless the maneuvers had previously been performed and the patient is no longer accessible for consent).

Note: Other protocol defined Inclusion/Exclusion criteria may apply.

Eligibility last updated 11/13/23. Questions regarding updates should be directed to the study team contact.