CPVT

Catecholaminergic polymorphic ventricular tachycardia (CPVT) is a rare inherited heart rhythm disorder characterized by episodes of irregular heartbeats triggered by physical activity or emotional stress. In CPVT, resting electrocardiograms are typically normal, and symptoms may include fainting or sudden loss of consciousness during exercise or excitement. The arrhythmias are often polymorphic or bidirectional ventricular tachycardia, which can progress to life-threatening rhythms if not treated.

Most cases arise from autosomal dominant mutations that affect calcium handling in cardiac cells, most commonly in the RYR2 gene, with autosomal recessive mutations in CASQ2 also described. Other related genes involved in calcium regulation have been implicated in smaller subsets. The underlying pathophysiology involves abnormal calcium release from the sarcoplasmic reticulum during sympathetic stimulation, leading to afterdepolarizations and triggered activity that can initiate ventricular tachycardia.

Diagnosis relies on clinical presentation and genetic testing. Resting ECG is usually normal; exercise or catecholamine challenge testing can provoke the characteristic bidirectional or polymorphic VT. Genetic testing confirms the diagnosis and informs family screening, since CPVT is inherited and relatives may be affected even without symptoms.

Management aims to prevent arrhythmias and sudden death. First-line therapy is nonselective beta-blockers (for example nadolol or propranolol). Flecainide may be added in some cases. Left cardiac sympathetic denervation and, in select patients, implantable cardioverter-defibrillators, are considered for refractory or high-risk individuals. Patients should avoid drugs that increase sympathetic activity and limit strenuous exercise, with regular follow-up and genetic counseling recommended.

CPVT carries a risk of sudden cardiac death, especially in the young, but prognosis improves with appropriate therapy and monitoring.