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Case 008: CPVT - Exertional Syncope and Palpitations

Presentation

A 14-year-old female is referred after syncopal episode during soccer practice. She reports feeling palpitations then "everything went black." Teammates report she fell and had brief jerking movements, then woke up confused.

History: - No prior syncope - No chest pain - No family history of sudden death (parents unaware of extended family) - Previously healthy, no medications

Vital Signs: - Heart rate: 72 bpm - Blood pressure: 110/68 mmHg - Normal physical exam

Initial Workup

Resting ECG: Normal sinus rhythm, QTc 420 ms, normal intervals

Echocardiogram: Structurally normal heart, normal LV function

Clinical Reasoning

Question 1: Why is this syncope concerning?

Answer **EXERTIONAL syncope is a cardiac RED FLAG** Concerning features: - Syncope DURING exercise (not after) - Palpitations preceding event - Brief convulsive activity (suggests cerebral hypoperfusion) - No prodrome of typical vasovagal Even with normal resting ECG and echo, channelopathy remains on differential.

Question 2: What additional testing is needed?

Answer **Exercise stress test** - CRITICAL for this presentation Looking for: - Exercise-induced ventricular arrhythmias - Specifically: **bidirectional or polymorphic VT** = CPVT Also consider: - Holter monitor - Event monitor (if episodes ongoing) - Genetic testing (can be done early if high suspicion)

Stress Test Results

Exercise stress test findings: - Frequent PVCs beginning at moderate exercise - Bigeminy at peak exercise - Bidirectional ventricular tachycardia at peak heart rate - Symptoms reproduced (palpitations, lightheaded) - Resolved with rest

Question 3: What is the diagnosis?

Answer **Catecholaminergic Polymorphic Ventricular Tachycardia (CPVT)** Diagnostic features: - Structurally normal heart - Normal resting ECG - Exercise/catecholamine-induced ventricular arrhythmias - **Bidirectional VT is pathognomonic** (alternating QRS axis) - Polymorphic VT also seen CPVT is HIGH RISK for sudden cardiac death (30-50% if untreated).

Question 4: What genetic testing should be sent?

Answer **CPVT genetic panel:** Most common genes: - **RYR2** (60-75% of CPVT) - autosomal dominant - **CASQ2** (~5%) - autosomal recessive Testing is indicated because: 1. Confirms diagnosis 2. Guides family screening 3. May have prognostic implications Genetic counseling should accompany testing.

Management

Question 5: What is the treatment?

Answer **First-line: Beta-blocker** - Nadolol (preferred - longest acting) - Propranolol (alternative) - Must be maximized to tolerance **Dosing:** - Nadolol: 1-2 mg/kg/day (max 2.5 mg/kg/day or ~160-240mg) - Target: HR response blunted on exercise **Adjunctive:** - **Flecainide** - add if breakthrough events or inadequate control on beta-blocker alone - Works by blocking RyR2 receptor - Not as monotherapy **ICD:** - Secondary prevention (survivors of arrest) - Consider if breakthrough events despite optimal medical therapy - ICD shocks can trigger catecholamine surge → VT storm (concern!) **Left cardiac sympathetic denervation (LCSD):** - For refractory cases or ICD storm

Question 6: What activity restrictions apply?

Answer **Strict activity restrictions:** - No competitive sports - Avoid strenuous exercise, especially adrenergic triggers - Avoid swimming alone (drowning risk if arrhythmia) - Avoid sudden startle, stress **Per 2025 guidelines:** - CPVT is one condition where restrictions remain firm - NOT included in shared decision-making for competitive sports participation - Lifelong restrictions

Genetic Results

Testing returns positive for RYR2 pathogenic variant.

Question 7: What cascade screening is needed?

Answer **All first-degree relatives:** - Genetic testing for the specific RYR2 variant - Even if genetic test negative, consider exercise stress test (incomplete penetrance) **If positive:** - Full cardiac evaluation - Exercise stress test - Consider prophylactic beta-blocker even if asymptomatic with positive test RYR2 mutations are autosomal dominant with variable penetrance.

Teaching Points

  1. Exertional syncope = cardiac until proven otherwise
  2. Normal resting ECG does NOT exclude CPVT - stress test essential
  3. Bidirectional VT is pathognomonic for CPVT
  4. Beta-blockers are first-line; flecainide can be added
  5. High SCD risk (30-50%) if untreated
  6. ICD can be problematic - shocks trigger more arrhythmias
  7. Strict activity restrictions - not eligible for shared decision-making