Catecholaminergic polymorphic ventricular tachycardia

• Individuals with catecholaminergic polymorphic ventricular tachycardia (CPVT) may be asymptomatic, or they may present with palpitations, syncope or sudden death.
• Affected individuals usually present in the first decade of life or during adolescence, often with syncope – although for some the first event may be sudden death.
• CPVT is characterised by episodes of ventricular tachycardia (bidirectional or polymorphic ventricular tachycardia) triggered by exercise or intense emotion. The ventricular tachycardia may spontaneously subside, or it may progress to ventricular fibrillation and cardiac arrest. There is a significant risk of ventricular arrhythmia, with up to 30% of affected individuals experiencing at least one cardiac arrest.

• CPVT is associated with pathogenic variants in the cardiac ryanodine receptor gene (RYR2) and cardiac calsequestrin gene (CASQ2). These genes are largely responsible for intracellular calcium handling.
• Pathogenic variants in other genes, such as CALM1, CALM2, CALM3, TRDN and TECR, have been identified in patients with clinical features similar to CPVT (often considered atypical CPVT).

• CPVT caused by pathogenic variants in the RYR2, CALM1, CALM2 and CALM3 genes is inherited in an autosomal dominant pattern. CPVT caused by pathogenic variants in the TECRL and TRDN genes is inherited in an autosomal recessive pattern.
• CPVT caused by pathogenic variants in the CASQ2 gene is typically inherited in an autosomal recessive pattern; however, there are rare cases in which it appears to be inherited in an autosomal dominant pattern, so heterozygous individuals should still undergo clinical screening.
• CPVT may also present de novo, with no clear family history.
• All first-degree relatives of an affected individual should be offered clinical screening. Where the pathogenic genetic variant is known, other family members should be offered predictive screening as part of cascade genomic testing.

• Where possible, affected individuals should avoid competitive sport, strenuous exercise and stressful environments.
• The first-line medical therapy is a nonselective beta blocker (for example, nadolol or propranolol).
• Flecainide can be added if cardiac arrhythmia persists during exercise testing on high-dose beta blocker therapy.
• Left cardiac sympathetic denervation should be considered for affected individuals who cannot tolerate beta blockers, or who have recurrent syncope or ventricular arrhythmias despite maximal medical therapy.
• An implantable cardioverter-defibrillator, in addition to beta blockers (with or without flecainide), should be considered for individuals with a history of cardiac arrest or recurrent syncope or ventricular arrhythmias despite maximal medical therapy.
• Individuals with CPVT should be considered for genomic counselling (see the National Genomic Test Directory for eligibility criteria).

For clinicians

• NHS England: National Genomic Test Directory

References:

• Zeppenfeld K, Tfelt-Hansen J, de Riva M and others. ‘2022 ESC guidelines for the management of patients with ventricular arrhythmias and the prevention of sudden cardiac death: Developed by the task force for the management of patients with ventricular arrhythmias and the prevention of sudden cardiac death of the European Society of Cardiology (ESC) endorsed by the Association for European Paediatric and Congenital Cardiology (AEPC)‘. European Heart Journal 2022: volume 43, issue 40, pages 3,997–4,126. DOI: 10.1093/eurheartj/ehac262

For patients

• British Heart Foundation: Catecholaminergic polymorphic ventricular tachycardia
• Cardiac Risk in the Young