Key Facts

Arrhythmogenic right ventricular cardiomyopathy (ARVC) is an inherited cardiomyopathy characterised by progressive fibro-fatty replacement of the right ventricular myocardium, creating an arrhythmogenic substrate that predisposes to ventricular tachycardia, VF, and sudden cardiac death, particularly during exercise.

Epidemiology

• Prevalence: ~1 in 2,000-5,000
• More common in males (clinical expression) ~3:1
• Mean age at presentation: 20-40 years
• Endemic in certain regions: Veneto region of Italy, Naxos disease (Greece)
• Second most common cause of SCD in young athletes after HCM

Aetiology

• Desmosomal gene mutations (~60% of cases):
  • PKP2 (plakophilin-2): most common (~40%)
  • DSG2 (desmoglein-2), DSP (desmoplakin), DSC2 (desmocollin-2), JUP (plakoglobin)
• Autosomal dominant with variable penetrance and expressivity
• Naxos disease: autosomal recessive (JUP mutation) — ARVC + palmoplantar keratoderma + woolly hair
• Carvajal syndrome: DSP mutation — LV-predominant ARVC + keratoderma + woolly hair

Pathophysiology

• Defective desmosomes (cell-cell junctions) → myocyte detachment and death
• Progressive fibro-fatty replacement of RV myocardium (RV free wall triangle of dysplasia: inflow, outflow, apex)
• Scar tissue creates re-entrant circuits → VT (typically LBBB morphology as arising from RV)
• Disease may progress to involve the LV (biventricular involvement)
• Exercise accelerates disease progression (increased mechanical stress on defective desmosomes)
• Concealed phase: structurally normal but electrically at risk → SCD may be first manifestation

Typical Presentation

• Palpitations (ventricular arrhythmias)
• Syncope (often exercise-related)
• Sudden cardiac death (may be first manifestation — often during sport)
• Heart failure (advanced disease with biventricular involvement)

Phases of Disease

1. Concealed phase: structurally normal heart; arrhythmic risk present
2. Overt electrical phase: structural changes on imaging; symptomatic arrhythmias
3. RV failure: progressive RV dilatation and dysfunction
4. Biventricular failure: LV involvement; resembles DCM

ECG Features

• T-wave inversions V1-V3 (beyond V1): most common finding; sensitivity ~85%
• Epsilon waves: small, low-amplitude positive deflections at the end of QRS in V1-V3 (pathognomonic but only in ~30%)
• Prolonged S-wave upstroke ≥55 ms in V1-V3
• VT with LBBB morphology (arises from RV)

Red Flags

• VT or cardiac arrest during exercise in a young person
• Family history of ARVC or juvenile SCD
• Progressive RV dilatation on echo
• Epsilon waves on ECG

Bedside

• 12-lead ECG: T-wave inversions V1-V3, epsilon waves, prolonged S-wave upstroke
• Signal-averaged ECG: late potentials (indicates delayed conduction through scar)

Bloods

• Routine: FBC, U&Es
• BNP: elevated in RV failure
• Genetic testing: desmosomal gene panel (PKP2, DSG2, DSP, DSC2, JUP)

Imaging

• Cardiac MRI (gold standard): RV dilatation, regional wall motion abnormalities (akinesia, dyskinesia, dyssynchrony), fibro-fatty replacement (may show fat on T1, LGE), LV involvement assessment
• Echocardiography: RV dilatation, RVOT dilatation, wall motion abnormalities (less sensitive than MRI)
• RV angiography: rarely performed; can show 'stack of coins' appearance

Special Tests

• Holter monitor (24-48 hours): >500 PVCs/24 hours (major criterion); NSVT or sustained VT
• Exercise testing: exercise-induced arrhythmias
• EP study: inducibility of VT
• Endomyocardial biopsy: fibro-fatty replacement — limited by sampling error (disease is patchy)

2010 Task Force Criteria

• Combination of major and minor criteria across 6 categories:
  1. Structural (MRI/echo): RV akinesia/dyskinesia + dilatation
  2. Histological: fibro-fatty replacement on biopsy
  3. Repolarisation: T-wave inversions V1-V3
  4. Depolarisation: epsilon waves, late potentials
  5. Arrhythmias: sustained VT with LBBB, >500 PVCs/24h
  6. Family history: confirmed ARVC in relative, SCD <35, pathogenic mutation
• Definite: 2 major, or 1 major + 2 minor, or 4 minor criteria

Non-pharmacological

• Exercise restriction: avoid competitive sport, endurance exercise, and high-intensity training — exercise accelerates disease
• Family screening: ECG, echo, MRI, genetic cascade testing for first-degree relatives
• Genetic counselling

Pharmacological

• Beta-blockers: first-line for arrhythmia suppression
• Sotalol or amiodarone: for VT suppression if beta-blocker inadequate
• Flecainide: adjunctive therapy combined with beta-blocker
• Heart failure therapy: standard HF medications if LV dysfunction develops
• Anticoagulation: if AF or significant RV dilatation with thrombus risk

Surgical/Interventional

• ICD implantation: for:
  • Cardiac arrest survivors (secondary prevention — class I)
  • Sustained VT
  • Severe RV/LV dysfunction
  • High-risk features on risk stratification
• Catheter ablation of VT: for recurrent VT despite medications; palliative (epicardial approach often needed; high recurrence)
• Heart transplantation: end-stage biventricular failure

Referral Criteria

• All suspected ARVC: inherited cardiac conditions service
• Cardiac arrest survivors: urgent ICD assessment
• Family screening: genetics clinic
• Progressive RV/biventricular failure: advanced HF team

• Annual mortality: ~1-3% with modern management (ICD)
• Without treatment: significant risk of SCD, especially during exercise
• ICD reduces SCD risk effectively; appropriate ICD therapy rate ~10% per year
• Progressive RV failure: occurs in ~30% over long-term follow-up
• Biventricular involvement: poorer prognosis, may require transplant
• LMNA and DSP mutations: associated with early LV involvement and worse outcomes
• With exercise restriction and appropriate management: most patients have reasonable long-term outcomes

2010 Task Force Criteria Categories

Triangle of Dysplasia