Disease Directory Catecholaminergic Polymorphic Ventricular Tachycardia
Cardiovascular

Catecholaminergic Polymorphic Ventricular Tachycardia

Also known as: CPVT, catecholaminergic VT, RYR2 channelopathy

Prevalence

1 per 10,000

Onset

Childhood or adolescence

Type

Autosomal dominant (RYR2); autosomal recessive (CASQ2)

Gene

RYR2, CASQ2

About Catecholaminergic Polymorphic Ventricular Tachycardia

Catecholaminergic Polymorphic Ventricular Tachycardia is a severe inherited arrhythmia syndrome in which adrenergic stimulation during exercise or emotional stress triggers bidirectional or polymorphic ventricular tachycardia, leading to syncope and sudden cardiac death in structurally normal hearts. Mutations in RYR2, encoding the cardiac ryanodine receptor responsible for intracellular calcium release during excitation-contraction coupling, account for the majority of cases, with recessive mutations in CASQ2 (calsequestrin 2) responsible for a smaller proportion. The arrhythmia is highly reproducible on exercise stress testing, which is both the key diagnostic tool and a monitoring method used in clinical trials.

Common Clinical Features

Exercise or emotion-triggered syncope, often in childhood Bidirectional or polymorphic ventricular tachycardia on stress testing Sudden cardiac arrest, frequently as the first manifestation Palpitations during physical activity Normal resting ECG and normal cardiac structure on imaging Ventricular ectopy triggered at predictable heart rate thresholds Family history of exercise-related sudden death Seizures misattributed to epilepsy in some children

Clinical Trial Eligibility Tips

What to know before applying to Catecholaminergic Polymorphic Ventricular Tachycardia trials.

Exercise stress testing is the definitive diagnostic tool and is used as a primary outcome measure in CPVT trials; a baseline graded exercise test with continuous ECG monitoring is typically required.

Genetic confirmation of RYR2 or CASQ2 pathogenic variants is important; given the implications for family members, cascade genetic testing should be performed before trial screening.

Current treatment with beta-blockers and flecainide is standard of care; many trials require patients to be on maximally tolerated medical therapy before enrolment, so document dosing history.

Patient Resources

Patient Organization

Sudden Arrhythmia Death Syndromes Foundation

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Natural History Registry

SADS Foundation Patient Registry

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Orphanet

European reference resource for rare diseases (ORPHA:3286)

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NORD

National Organization for Rare Disorders

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Find recruiting Catecholaminergic Polymorphic Ventricular Tachycardia trials

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