Nationwide experience of catecholaminergic polymorphic ventricular tachycardia caused by RyR2 mutations

Area of Science:

• Cardiology
• Genetics
• Electrophysiology

Background:

• Catecholaminergic polymorphic ventricular tachycardia (CPVT) is a genetic disorder characterized by stress-induced ventricular arrhythmias.
• Mutations in the ryanodine receptor-2 (RyR2) gene are a primary cause of CPVT.
• Understanding disease penetrance and clinical course is crucial for patient management.

Purpose of the Study:

• To characterize disease penetrance, clinical course, and treatment strategies in a nationwide cohort of Danish patients with RyR2-related CPVT.
• To evaluate the use of antiarrhythmic medication and implantable cardioverter-defibrillator (ICD) therapy.

Main Methods:

• A Danish nationwide cohort of patients with RyR2 mutations was identified through the national hereditary heart disease database.
• The cohort was stratified into probands, symptomatic relatives, and asymptomatic relatives.
• Data on presenting symptoms, age at onset, fatal/near-fatal events, and ICD therapy were analyzed.

Main Results:

• 23 probands and 28 relatives (18 symptomatic, 10 asymptomatic) with RyR2 mutations were identified.
• 87% of probands and 36% of relatives experienced severe presenting symptoms (sudden cardiac death, aborted SCD, syncope).
• Probands had a significantly earlier age at onset (16 vs. 43 years) and higher risk of fatal/near-fatal events compared to symptomatic relatives.

Conclusions:

• RyR2 mutation-positive CPVT patients, including relatives identified through screening, frequently present with severe cardiac events.
• Probands exhibit a more severe clinical phenotype with earlier onset and increased risk of life-threatening arrhythmias.
• ICD therapy was utilized, with appropriate shocks in a subset of patients, highlighting the need for vigilant management.