What are the recommended management and treatment options for an individual who is a carrier of Arrhythmogenic Right Ventricular Cardiomyopathy (ARVC)?

Management of ARVC Genetic Carriers

If you are a genetic carrier of ARVC with a pathogenic mutation but no clinical manifestations, you require clinical screening and surveillance but not necessarily treatment—however, beta-blockers and exercise restriction should be strongly considered even in asymptomatic carriers given the progressive nature of the disease. 1

Initial Evaluation and Screening

All first-degree relatives of ARVC patients should undergo comprehensive clinical screening, which is a Class I recommendation 2:

• 12-lead ECG to detect T-wave inversions in right precordial leads (V1-V3), epsilon waves, or prolonged terminal activation duration >55ms 2, 1
• Echocardiography to assess right and left ventricular function and detect structural abnormalities 2
• Cardiac MRI is the most useful imaging modality for establishing diagnosis and risk stratification, particularly for detecting RV wall thinning, aneurysms, and fibrofatty replacement 2, 1, 3
• Signal-averaged ECG can be useful for diagnosis and risk stratification 2, 1
• Ambulatory ECG monitoring to detect ventricular arrhythmias, as up to two-thirds of patients have ventricular arrhythmias on monitoring 1

Genetic Testing and Counseling

Genetic counseling and testing are reasonable (Class IIa) for diagnosis and gene-specific targeted family screening 2, 1:

• If the proband has an identified disease-causing mutation, genetic testing of first-degree relatives is recommended (Class I) 2, 1
• Most cases are inherited as autosomal dominant with mutations in desmosomal proteins (plakophilin, desmoplakin) 2, 1
• Approximately 60% of index patients have identifiable pathogenic mutations 3

Management for Asymptomatic Carriers

Exercise Restriction

Avoidance of competitive sports and intensive exercise is recommended (Class I) for all patients with clinically diagnosed ARVC, even if asymptomatic 2, 1:

• This is a Class I recommendation despite being based on observational data, reflecting the high risk of sudden cardiac death during exertion 1
• Exercise can accelerate disease progression and trigger arrhythmias in genetically susceptible individuals 1

Beta-Blocker Therapy

Beta-blockers can be useful (Class IIa) in patients with clinical evidence of ARVC but without ventricular arrhythmias 2:

• Beta-blockers are recommended (Class I) if ventricular arrhythmias develop 2, 1
• They serve as first-line antiarrhythmic therapy 1, 4

Surveillance Strategy

Asymptomatic carriers require periodic reassessment since ARVC is a progressive disease 1:

• Repeat clinical evaluation including ECG and imaging at regular intervals (typically annually or biannually)
• Risk stratification should be performed at initial evaluation and periodically thereafter 2
• Clinical manifestations typically develop between the second and fourth decades of life 1, 3

Risk Stratification

Electrophysiological study may be considered (Class IIb) for risk stratification in asymptomatic patients with clinical evidence of ARVC, though its role remains poorly defined 2, 1:

Risk factors for sudden cardiac death include 1:

• History of aborted sudden cardiac death
• Documented sustained VT or poorly tolerated VT
• Unexplained syncope
• Frequent nonsustained VT
• Family history of premature sudden death
• Extensive RV disease or LV involvement
• Marked QRS prolongation
• Late gadolinium enhancement on CMR

ICD Considerations for Carriers

ICD implantation is NOT routinely recommended for asymptomatic genetic carriers without clinical manifestations 2:

ICD is recommended (Class I) only when 2, 1:

• Resuscitated sudden cardiac arrest
• Sustained VT causing syncope or hemodynamic compromise
• Significant ventricular dysfunction (RVEF or LVEF ≤35%)

ICD is reasonable (Class IIa) for 2, 1:

• Syncope presumed due to ventricular arrhythmia
• Extensive disease including left ventricular involvement
• One or more affected family members with sudden cardiac death

Key Clinical Pitfalls

Common mistake: Assuming genetic carriers without clinical manifestations require immediate ICD implantation—this is incorrect as ICD is reserved for those with documented arrhythmias or high-risk features 2, 1

Important caveat: Left ventricular involvement occurs in >50% of patients with ARVC, so assessment should not focus solely on the right ventricle 1

Critical consideration: Disease progression may occur despite normal initial evaluation, making ongoing surveillance essential rather than a single assessment 1, 4