Arrhythmogenic Right Ventricular Dysplasia (ARVD/ARVC) Management and Diagnosis

Definition and Pathophysiology

• The European Society of Cardiology states that 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, according to the European Heart Journal 1, 2
• Prevalence is estimated at 1 in 1,000 to 1 in 5,000 in the general population, as reported by the European Heart Journal 1, 2
• Clinical manifestations typically develop between the second and fourth decades of life, as stated by the European Heart Journal 1, 2
• ARVD is an important cause of sudden cardiac death in athletes and young adults, according to the European Heart Journal 1, 2

Genetics and Inheritance

• Most cases are inherited as autosomal dominant with mutations in genes encoding desmosomal proteins, as reported by the European Heart Journal 1, 2
• Rare recessive forms exist, associated with palmar and plantar hyperkeratosis, according to the European Heart Journal 1, 2
• The American Heart Association recommends genetic counseling and testing for diagnosis and gene-specific targeted family screening in clinically diagnosed or suspected cases 3, 4
• First-degree relatives should undergo clinical screening including ECG, echocardiography, and genetic testing if the proband has an identified mutation, as stated by the American Heart Association 3, 4

Diagnosis

• The Task Force criteria incorporate histological, genetic, electrocardiographic, and imaging parameters to classify patients into definite, borderline, and possible categories, as reported by the European Heart Journal 1, 2
• Cardiac MRI is useful for establishing diagnosis and risk stratification in patients with suspected ARVD and ventricular arrhythmias or ECG abnormalities, according to the American Heart Association 3, 4
• Signal-averaged ECG can be useful for diagnosis and risk stratification, as stated by the American Heart Association 3, 4
• Up to two-thirds of patients have ventricular arrhythmias on resting or ambulatory ECG monitoring and exercise testing, as reported by the European Heart Journal 1, 2

Management Strategy

• The European Society of Cardiology recommends avoidance of competitive sports in all patients with ARVD, as this is a Class I recommendation despite being based on observational data 1, 2, 3, 4
• Beta-blockers are recommended as first-line therapy in patients with ARVD and ventricular arrhythmias, according to the American Heart Association 3, 4
• Amiodarone was superior to beta-blockers and sotalol in preventing ventricular arrhythmias in observational studies, as reported by the European Heart Journal 1, 2
• ICD implantation is recommended for prevention of sudden cardiac death in patients with ARVD and documented sustained VT or VF, as stated by the European Heart Journal 5, 6, 7

ICD Therapy

• The American Heart Association recommends ICD implantation 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 3, 4
• Class I indications for ICD include resuscitated sudden cardiac arrest, sustained ventricular tachycardia, and significant ventricular dysfunction, as reported by the American Heart Association 3, 4
• Class IIa indications for ICD include syncope presumed due to ventricular arrhythmia, extensive disease including left ventricular involvement, and one or more affected family members with sudden cardiac death, as stated by the European Heart Journal 5, 6, 7

Catheter Ablation

• The American Heart Association recommends catheter ablation for patients with recurrent symptomatic sustained VT despite optimal medical therapy, primarily to reduce arrhythmia frequency and prevent ICD shocks, as reported by the European Heart Journal 1, 2, 3, 4
• Combined endocardial/epicardial approach can be beneficial when beta-blockers are ineffective or not tolerated, according to the American Heart Association 3, 4
• Epicardial ablation may increase success rates, as stated by the European Heart Journal 1, 2

Risk Stratification

• Electrophysiological study may be considered for risk stratification in asymptomatic patients with clinical evidence of ARVD, though its role remains poorly defined, as reported by the American Heart Association 3, 4
• Risk factors for sudden cardiac death or appropriate ICD discharge include history of aborted sudden cardiac death, poorly tolerated VT and syncope, documented sustained VT, unexplained syncope, frequent nonsustained VT, family history of premature sudden death, extensive RV disease, marked QRS prolongation, late gadolinium enhancement on CMR including LV involvement, and LV dysfunction, as stated by the European Heart Journal 8

Prognosis

• Annual mortality rates vary considerably depending on cohort characteristics, as reported by the European Heart Journal 1, 2
• Meta-analysis data show annualized rates of 0.9% for cardiac mortality, 0.8% for non-cardiac mortality, and 0.9% for heart transplantation, according to the European Heart Journal 1, 2
• Disease progression may result in right or biventricular heart failure requiring transplantation, as stated by the European Heart Journal 1, 2

Management of ARVC Genetic Carriers

Initial Evaluation and Screening

• The American Heart Association recommends that all first-degree relatives of ARVC patients undergo comprehensive clinical screening, which includes a 12-lead ECG to detect T-wave inversions in right precordial leads, epsilon waves, or prolonged terminal activation duration, as a Class I recommendation 9, 10
• Echocardiography is recommended to assess right and left ventricular function and detect structural abnormalities, as a Class I recommendation 9, 10
• Cardiac MRI is the most useful imaging modality for establishing diagnosis and risk stratification, particularly for detecting RV wall thinning, aneurysms, and fibrofatty replacement, as a Class I recommendation 9

Genetic Testing and Counseling

• Genetic counseling and testing are reasonable for diagnosis and gene-specific targeted family screening, as a Class IIa recommendation, with most cases being inherited as autosomal dominant with mutations in desmosomal proteins, according to the American College of Cardiology 9, 11

Management for Asymptomatic Carriers

• The American College of Cardiology recommends avoidance of competitive sports and intensive exercise for all patients with clinically diagnosed ARVC, even if asymptomatic, as a Class I recommendation 9
• Beta-blockers can be useful in patients with clinical evidence of ARVC but without ventricular arrhythmias, as a Class IIa recommendation, and are recommended if ventricular arrhythmias develop, as a Class I recommendation, according to the American College of Cardiology 9

ICD Considerations for Carriers

• ICD implantation is NOT routinely recommended for asymptomatic genetic carriers without clinical manifestations, but is recommended for those with resuscitated sudden cardiac arrest, sustained VT causing syncope or hemodynamic compromise, or significant ventricular dysfunction, as a Class I recommendation, according to the American College of Cardiology 9
• ICD is reasonable for syncope presumed due to ventricular arrhythmia, extensive disease including left ventricular involvement, or one or more affected family members with sudden cardiac death, as a Class IIa recommendation, according to the American College of Cardiology 9, 11