What is the management of Arrhythmogenic Right Ventricular Dysplasia (ARVD)?

Arrhythmogenic Right Ventricular Dysplasia (ARVD/ARVC)

Definition and Pathophysiology

ARVD is a progressive inherited heart muscle disorder characterized by replacement of cardiomyocytes with adipose and fibrous tissue, leading to ventricular arrhythmias, heart failure, and sudden cardiac death. 1

• The disease primarily affects the right ventricle structurally, but left ventricular involvement occurs in >50% of patients 1
• Prevalence is estimated at 1 in 1,000 to 1 in 5,000 in the general population 1
• Clinical manifestations typically develop between the second and fourth decades of life 1
• ARVD is an important cause of sudden cardiac death in athletes and young adults 1

Genetics and Inheritance

• Most cases are inherited as autosomal dominant with mutations in genes encoding desmosomal proteins: plakoglobin, desmoplakin, plakophilin-2, desmoglein-2, and desmocollin-2 1
• Rare recessive forms exist (Carvajal syndrome and Naxos disease) associated with palmar and plantar hyperkeratosis 1
• Genetic counseling and testing are reasonable for diagnosis and gene-specific targeted family screening in clinically diagnosed or suspected cases 1
• First-degree relatives should undergo clinical screening including ECG, echocardiography, and genetic testing if the proband has an identified mutation 1

Diagnosis

Diagnosis is established using Task Force criteria incorporating histological, genetic, electrocardiographic, and imaging parameters to classify patients into definite, borderline, and possible categories. 1

Key Diagnostic Modalities:

• Cardiac MRI is useful for establishing diagnosis and risk stratification in patients with suspected ARVD and ventricular arrhythmias or ECG abnormalities 1
• Signal-averaged ECG can be useful for diagnosis and risk stratification 1
• Up to two-thirds of patients have ventricular arrhythmias on resting or ambulatory ECG monitoring and exercise testing 1
• Ventricular arrhythmias typically show left bundle branch morphology (RV origin) with QRS axis differing from RVOT tachycardia 1

Management Strategy

Exercise Restriction (Class I Recommendation)

Avoidance of competitive sports is mandatory in all patients with ARVD. 1

• Endurance training at competitive levels exacerbates the ARVD phenotype 1
• This is a Class I, Level C recommendation despite lack of controlled trials 1

Medical Therapy for Arrhythmias

Beta-blockers are recommended as first-line therapy in patients with ARVD and ventricular arrhythmias. 1

• Beta-blockers (particularly sotalol) are conventionally recommended for frequent ventricular ectopy or nonsustained VT, though recent observational data suggest limited efficacy 1
• Amiodarone was superior to beta-blockers and sotalol in preventing ventricular arrhythmias in observational studies 1
• Amiodarone or sotalol can be effective for sustained VT/VF when ICD implantation is not feasible 1
• Beta-blockers can be useful even in patients with clinical evidence of ARVD but without documented ventricular arrhythmias 1

ICD Therapy - The Cornerstone of Management

ICD implantation is recommended for prevention of sudden cardiac death in patients with ARVD and documented sustained VT or VF who have reasonable expectation of survival with good functional status for >1 year. 1

Class I Indications for ICD:

• Resuscitated sudden cardiac arrest 1
• Sustained ventricular tachycardia 1
• Significant ventricular dysfunction with RVEF or LVEF ≤35% 1

Class IIa Indications for ICD:

• Syncope presumed due to ventricular arrhythmia 1
• Extensive disease including left ventricular involvement 1
• One or more affected family members with sudden cardiac death 1
• Undiagnosed syncope when VT/VF has not been excluded 1

Important caveat: The annualized appropriate ICD intervention rate is 9.5%, but inappropriate shocks occur at 3.7% annually, with lead complications in 18.4% of cases 1

Catheter Ablation

Catheter ablation should be considered in experienced centers for patients with recurrent symptomatic sustained VT despite optimal medical therapy, primarily to reduce arrhythmia frequency and prevent ICD shocks—not to improve prognosis. 1

• Combined endocardial/epicardial approach can be beneficial when beta-blockers are ineffective or not tolerated 1
• Acute suppression is more successful in patients with single or few dominant VT morphologies 1
• Epicardial ablation may increase success rates 1
• Critical limitation: Neither antiarrhythmic drugs nor catheter ablation provides sufficient protection against sudden cardiac death 1
• Ablation is adjunctive therapy for recurrent VT despite optimal antiarrhythmic therapy 1

Risk Stratification

Electrophysiological study may be considered for risk stratification in asymptomatic patients with clinical evidence of ARVD, though its role remains poorly defined. 1

Risk factors for sudden cardiac death or appropriate ICD discharge include:

• History of aborted sudden cardiac death (highest risk, up to 10% per annum) 1
• Poorly tolerated VT and syncope 1
• Documented sustained VT 1
• Unexplained syncope 1
• Frequent nonsustained VT 1
• Family history of premature sudden death 1
• Extensive RV disease 1
• Marked QRS prolongation 1
• Late gadolinium enhancement on CMR including LV involvement 1
• LV dysfunction 1

Prognosis

• Annual mortality rates vary considerably depending on cohort characteristics 1
• Meta-analysis data show annualized rates of 0.9% for cardiac mortality, 0.8% for non-cardiac mortality, and 0.9% for heart transplantation 1
• Disease progression may result in right or biventricular heart failure requiring transplantation 1

Common Pitfalls to Avoid

• Do not rely on catheter ablation or antiarrhythmic drugs alone for sudden death prevention—ICD remains the primary protective strategy 1
• Do not allow patients to continue competitive athletics—this is a firm Class I recommendation despite being based on observational data 1
• Do not assume genetic testing contributes to risk stratification—it is useful for family screening but not for individual risk assessment 1
• Be aware that difficult ICD lead placement occurs in 18.4% of cases due to RV structural abnormalities 1