Can you give me a quick overview of catecholaminergic polymorphic ventricular tachycardia (CPVT)?

Catecholaminergic Polymorphic Ventricular Tachycardia (CPVT): Quick Overview

CPVT is a rare inherited arrhythmia syndrome where exercise or emotional stress triggers life-threatening bidirectional or polymorphic ventricular tachycardia in patients with structurally normal hearts and normal resting ECGs. 1

Definition and Epidemiology

• CPVT is diagnosed when a structurally normal heart and normal ECG are present alongside exercise- or emotion-induced bidirectional or polymorphic VT. 1
• The disease has an estimated prevalence of 1 in 10,000. 1
• Clinical manifestations typically occur in the first decade of life, though late-onset cases exist. 1
• CPVT is a significant cause of autopsy-negative sudden death in children and adolescents. 2

Genetic Basis

• Two main genetic types exist: an autosomal dominant variant due to mutations in the cardiac ryanodine receptor gene (RyR2), and a rare autosomal recessive variant caused by mutations in the cardiac calsequestrin gene (CASQ2). 1
• Approximately 50% of autosomal dominant cases are caused by RyR2 mutations. 1
• CPVT is diagnosed in patients who are carriers of pathogenic mutations in RyR2 or CASQ2 genes. 1
• Other genes (KCNJ2, Ank2, TRDN, CALM1) have been identified but their role as true CPVT phenocopies remains unclear. 1

Clinical Presentation

• Patients present with syncope, cardiac arrest, or sudden cardiac death triggered by physical activity or emotional stress. 1, 2
• The resting ECG and echocardiogram are characteristically normal, making diagnosis challenging. 1
• Patients typically have no ventricular extrasystoles or nonsustained VT on Holter monitoring at rest. 1
• The characteristic arrhythmia pattern is bidirectional VT (beat-to-beat alternating QRS axis changing by 180°), though irregular polymorphic VT or VF can also occur. 1

Diagnostic Approach

• An exercise stress test that elicits bidirectional or polymorphic VT is the cornerstone for establishing diagnosis. 1
• During exercise testing, isolated premature ventricular complexes typically precede runs of nonsustained VT, which increase in duration with continued exercise and may become sustained. 1
• Both supraventricular and ventricular arrhythmias are usually reproducibly induced by exercise stress testing. 1
• Catecholamine infusion has been suggested but its sensitivity is not clearly defined. 1
• Invasive electrophysiology studies with programmed ventricular stimulation are NOT recommended for risk stratification, as the arrhythmia is not inducible with programmed stimulation. 1

Risk Stratification

• Independent predictors for arrhythmic events include: diagnosis in childhood, lack of beta-blocker therapy, and persistence of complex arrhythmias during exercise stress testing on full-dose beta-blockers. 1
• Patients with a history of cardiac arrest are at highest risk. 1
• Recurrence of sustained VT, hemodynamically untolerated VT, or syncope while on beta-blockers indicates higher risk. 1

Treatment Algorithm

First-Line Therapy

• Exercise restriction and beta-blockers without intrinsic sympathomimetic activity are the first-line therapy. 1
• Most referral centers use nadolol, though comparative data on different beta-blockers are not available. 1
• Beta-blocker therapy should be considered for genetically positive family members, even after a negative exercise test. 1

Second-Line Therapy (Beta-Blocker Failure)

• Flecainide should be considered in addition to beta-blockers in patients who experience recurrent syncope or polymorphic/bidirectional VT while on beta-blockers. 1
• Flecainide significantly reduces ventricular arrhythmia burden and should be the first addition when arrhythmic control is incomplete. 1
• Flecainide should be considered in ICD carriers to reduce appropriate ICD shocks. 1

Third-Line Therapy

• Left cardiac sympathetic denervation may be considered in patients who experience recurrent syncope or polymorphic/bidirectional VT/several appropriate ICD shocks while on beta-blockers or beta-blockers plus flecainide. 1
• This procedure may also be considered in patients intolerant or with contraindications to beta-blockers. 1
• More data and longer follow-up are needed to fully quantify its efficacy. 1

ICD Therapy

• Survivors of cardiac arrest should receive beta-blockers and an ICD; flecainide should also be considered if arrhythmic control on exercise stress testing is incomplete. 1
• An ICD should be considered in patients who do not respond to beta-blockers and flecainide. 1
• If syncope occurs in a patient taking a beta-blocker, ICD implantation is recommended. 1
• Critical caveat: The ICD should be programmed with long delays before shock delivery, because painful shocks increase sympathetic tone and trigger further arrhythmias, leading to a malignant cycle of ICD shocks and even death. 1
• Concerns exist about ICD efficacy and the risk of catecholamine-driven proarrhythmic storms. 2

Important Clinical Pitfalls

• Beta-blockers may be effective in preventing syncope even when arrhythmias can still be elicited during exercise stress testing. 1
• Various attempts at cardioversion, lidocaine, and magnesium sulfate may be only partially effective during acute episodes; intravenous propranolol can achieve immediate VT interruption. 3
• Electrophysiological testing is not useful in management since the arrhythmia is not inducible with programmed ventricular stimulation. 1