Catecholaminergic polymorphic ventricular tachycardia in young athletes: a rare but potentially fatal disease

Background

Catecholaminergic polymorphic ventricular tachycardia (CPVT) is a primary electrical disease characterised by a normal resting electrocardiogram and induction of malignant arrhythmias during adrenergic stress leading to syncope or sudden cardiac death (SCD). This condition is most commonly associated with mutations in the cardiac ryanodine receptor (RyR2) or in the calsequestrin 2 genes (CASQ2). Mutations in RYR2 gene and CASQ2 gene are transmitted through autosomal dominant and autosomal recessive mode respectively, although an autosomal dominant transmission has been recently demonstrated also for CASQ2 mutations.

The homeostasis of intracellular calcium is affected by these mutations, resulting in triggered-activity polymorphic ventricular tachycardia favoured by adrenergic stimulation in the absence of structural abnormalities.

Catecholaminergic polymorphic ventricular tachycardia (CPVT) is characterized by a normal resting ECG and ventricular arrhythmias only during exercise or emotional triggers, typically in the form of polymorphic premature ventricular beats (PVBs), that increase in number and complexity with the increase of exercise intensity. Affected individuals may be asymptomatic, or experience symptoms that can range from palpitations to sudden cardiac death. The diagnosis may be difficult because arrhythmias are absent at rest and the heart is structurally normal; however, given the high risk of sudden cardiac death linked to this condition, the disease should be suspected in athletes with exercise-related ventricular arrhythmias or symptoms. Definite diagnosis relies on genetic testing.

Beta blockers therapy is the first-line therapy while high-intensity exercise should be avoided.

The case

A 41-year-old female athlete affected by CPVT with a particular double gene mutation

A 41-year-old female asymptomatic runner was diagnosed with CPVT after an exercise test performed during a pre-participation screening visit.

Despite a normal resting ECG, during exercise couplets and triplets of ventricular premature beats with right bundle branch block superior with axis morphology were identified. During an exercise session recording by a 12-lead 24 hours ECG, polymorphic premature ventricular beats were recorded (both left bundle branch block and right bundle branch block). The patient had always been asymptomatic and cardiac magnetic resonance showed no abnormalities.

However, because of the behaviour of the arrhythmias, genetic testing was performed which showed a heterozygous nonsense mutation of ryanodine gene (RYR2). In addition, all family members were screened and one of the two sons, as well as the sister and mother, were found to carry the same mutation, with different degree of phenotypic expression.