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Catecholaminergic Polymorphic Ventricular Tachycardia (CPVT) is a rare, genetic cardiac arrhythmia disorder characterized by an abnormal heart rhythm (ventricular tachycardia) in response to physical activity or emotional stress, despite a structurally normal heart. The condition is significant due to its association with a high risk of syncope (fainting) and sudden cardiac death in young individuals, including children and adolescents.

Etiology and Pathophysiology

CPVT is primarily caused by mutations in the RYR2 gene, which encodes the ryanodine receptor 2, a critical component of the cardiac calcium channel responsible for the regulation of calcium release from the sarcoplasmic reticulum into the cytoplasm of heart muscle cells. This mutation leads to an abnormal calcium release, which is the underlying mechanism for the arrhythmias seen in CPVT. Less commonly, mutations in the CASQ2 gene, encoding calsequestrin 2, a calcium-binding protein in the heart, can also cause CPVT. These genetic abnormalities result in an increased intracellular calcium concentration during adrenergic stimulation, leading to delayed afterdepolarizations and triggered activity that manifest as ventricular arrhythmias.

Clinical Presentation

Patients with CPVT typically present in childhood or adolescence with symptoms triggered by emotional stress or physical exercise. These symptoms include palpitations, dizziness, syncope, and in severe cases, sudden cardiac death. The diagnosis is often made through a combination of the patient's clinical history, family history, and the results of an exercise stress test, which can provoke the characteristic bidirectional or polymorphic ventricular tachycardia in individuals with CPVT.

Management

The management of CPVT focuses on preventing sudden cardiac death and includes both pharmacological and non-pharmacological strategies. Beta-blockers are the cornerstone of therapy, significantly reducing the risk of arrhythmic events. In some cases, where beta-blockers are insufficient, calcium channel blockers or flecainide may be added. For high-risk patients, or those who have experienced cardiac arrest, an implantable cardioverter-defibrillator (ICD) may be recommended. Lifestyle modifications, including avoidance of competitive sports and situations that may induce emotional stress, are also advised.

Genetic Counseling

Given the genetic nature of CPVT, genetic counseling is an important aspect of managing individuals and families affected by this condition. Identifying the specific genetic mutation allows for targeted testing of family members, which can identify at-risk individuals before the onset of symptoms, allowing for early intervention and management to prevent sudden cardiac death.