What is the recommended diagnostic work‑up for arrhythmogenic right ventricular dysplasia (ARVD) in a young adult or adolescent presenting with unexplained ventricular arrhythmias, syncope, or a family history of sudden cardiac death and abnormal right‑ventricular findings on ECG?

Diagnostic Work-up for Arrhythmogenic Right Ventricular Dysplasia (ARVD)

In a young adult or adolescent presenting with unexplained ventricular arrhythmias, syncope, or family history of sudden cardiac death with abnormal right ventricular findings, diagnosis requires systematic application of the Revised Task Force Criteria using multi-modality imaging, ECG analysis, arrhythmia documentation, and genetic testing. 1

Initial Clinical Evaluation

The diagnostic work-up should begin with specific red-flag symptom identification:

• Exercise-related palpitations or syncope
• Aborted sudden cardiac arrest, particularly during exercise
• Frequent ventricular ectopy (>500 in 24 hours)
• Ventricular tachycardia with left bundle branch block morphology 1

Obtain a detailed three-to-four-generation family pedigree focusing on sudden cardiac death, cardiomyopathy, and arrhythmias in relatives under age 40 1.

Core Diagnostic Testing Battery

Electrocardiographic Assessment

Perform the following ECG studies:

• 12-lead ECG looking for:

  • Right precordial T-wave inversions (V1-V3)
  • Low QRS voltages in peripheral leads
  • Terminal activation delay (epsilon waves) in right precordial leads
  • Lateral or inferolateral T-wave inversions (V5, V6, I, aVL) suggesting left ventricular involvement 1, 2

• Signal-averaged ECG for diagnosis and risk stratification (Class IIa recommendation) 1

• 24-hour Holter monitoring to quantify ventricular ectopy burden and document arrhythmias 2

• Exercise stress testing to provoke ventricular arrhythmias and assess exercise capacity 2

Multi-Modality Imaging Protocol

2D Echocardiography (first-line imaging):

• Quantitative assessment of right ventricular size and function
• Right ventricular outflow tract diameter measurement
• Evaluation for regional wall motion abnormalities
• Assessment for left ventricular involvement 1, 2

Cardiac Magnetic Resonance Imaging (essential for tissue characterization):

• Perform at baseline in all suspected cases
• Assess for right ventricular dilatation and dysfunction
• Late gadolinium enhancement (LGE) to detect myocardial scar - this is now a recognized diagnostic hallmark, particularly the "ring-like" pattern in left ventricular variants 3
• Evaluate for fibro-fatty replacement
• Document left ventricular involvement if present 2

CMR is particularly critical as it can detect tissue substrate for arrhythmias even when conventional wall motion abnormalities are absent 2.

Applying the Revised Task Force Criteria

The diagnosis is established using the 2010 International Task Force Criteria across six categories 1:

1. Right ventricular imaging abnormalities (echo/CMR)
2. Tissue characterization (endomyocardial biopsy if needed)
3. Repolarization abnormalities (ECG changes)
4. Depolarization/conduction abnormalities (epsilon waves, terminal activation delay)
5. Arrhythmias (documented ventricular tachycardia/ectopy)
6. Family history (including genetic testing)

Diagnostic Thresholds:

• Definite diagnosis: 2 major OR 1 major + 2 minor OR 4 minor criteria from different categories
• Borderline diagnosis: 1 major + 1 minor OR 3 minor criteria from different categories
• Possible diagnosis: 1 major OR 2 minor criteria from different categories 1

Genetic Testing Strategy

Offer genetic testing only after establishing high pre-test probability through clinical evaluation 4. This should be:

• Performed with appropriate pre- and post-test genetic counseling
• Focused on desmosomal genes (plakoglobin, desmoplakin, plakophilin-2, desmoglein-2, desmocollin) 5, 6
• Understood as the "final piece of the puzzle" - negative genetic testing does not exclude ARVD 4

First-degree relatives of patients with identified pathogenic variants should undergo genetic testing (Class I recommendation) 1.

Additional Diagnostic Modalities for Uncertain Cases

When diagnosis remains unclear after non-invasive testing:

• Endomyocardial biopsy: Major criterion if residual myocytes <60% with fibro-fatty replacement; minor criterion if 60-75% 2
• Electro-anatomical mapping: Identifies low-voltage areas corresponding to fibro-fatty tissue replacement, particularly useful for differentiating from idiopathic RVOT tachycardia 2
• Electrophysiology study: Consider in asymptomatic patients with clinical evidence of ARVC for risk stratification (Class IIb recommendation) 1

Critical Pitfalls to Avoid

Do not rely on a single diagnostic modality - ARVC has no pathognomonic finding 7. The strength of diagnosis comes from combining abnormalities across multiple categories.

Recognize left ventricular and biventricular variants - the 2010 Task Force Criteria primarily address right ventricular disease, but up to 50% of cases involve both ventricles 8. The 2024 European Task Force has proposed updated criteria specifically addressing left-sided variants 3.

Do not dismiss the diagnosis in females or older patients - while ARVC predominantly affects young males (3:1 ratio), females have milder phenotypes with later presentation, and diagnosis can occur at any age 4, 5.

Differentiate from phenocopies: Consider cardiac sarcoidosis (mediastinal lymphadenopathy, LV septal scar, PET-FDG uptake), myocarditis, dilated cardiomyopathy, and idiopathic RVOT tachycardia in the differential 2, 6.

Follow-up Imaging Strategy

Once baseline evaluation is complete:

• Definite ARVD without ICD: Echocardiography yearly; CMR every 3-5 years or when clinical changes occur 2
• Borderline/possible ARVD: Closer monitoring with echocardiography yearly and CMR every 1-2 years 2
• Mutation-positive family members: Echocardiography yearly starting at age 10; CMR at baseline and every 1-2 years if borderline findings, every 3-5 years if asymptomatic 2