Arrhythmogenic right ventricular cardiomyopathy (ARVC)

Definition

Arrhythmogenic right ventricular cardiomyopathy (ARVC), formerly arrhythmogenic right ventricular dysplasia (ARVD), is a genetic heart disease that mainly affects the right ventricle and causes ventricular tachyarrhythmias and an increased risk of sudden death. Variants are arrhythmogenic left ventricular (ALVC) and biventricular cardiomyopathy (ABVC); collectively the term arrhythmogenic cardiomyopathy is used.

Classification

Diagnostic criteria (task force)

An international task force has proposed major and minor criteria; depending on the combination, possible, borderline or definite disease of the right, left or both ventricles is diagnosed. The criteria include:

• imaging evidence of ventricular disease (often fibrous or fatty infiltration or replacement of myocardium)
• biopsy showing replacement of cardiomyocytes by fibrous and/or fatty tissue
• ECG repolarisation abnormalities, e.g. right precordial T-wave inversion
• ECG depolarisation abnormalities, e.g. right precordial epsilon waves
• late potentials on the signal-averaged ECG
• documented ventricular arrhythmias originating from scar (mostly right ventricular)
• family history of arrhythmogenic cardiomyopathy or sudden death
• identification of a disease-associated gene mutation

Occurrence & epidemiology

Frequency varies regionally between 1:2000 and 1:5000. ARVC and its variants account for about 10 % of sudden cardiac deaths not explained by coronary or other structural disease.

Aetiopathogenesis

• Genetics: mutations mostly affect desmosomal proteins of the intercalated discs that mechanically connect cardiomyocytes – e.g. plakophilin, desmoplakin and desmoglein. Inheritance is mostly autosomal dominant with variable penetrance; autosomal recessive forms occur.
• Pathogenesis: the abnormal cell junctions are damaged by mechanical stress; during healing, cardiomyocytes are replaced by fibrous and fatty tissue – predominantly in the triangle between the right ventricular outflow tract, inflow tract and apex, sometimes also in the posterolateral left ventricle.
• Course: initially ventricular ectopic beats and tachyarrhythmias predominate, later structural changes of the right ventricle (dilatation, wall thinning) up to heart failure.
• Sustained heavy exertion, such as endurance sport, is thought to hasten onset and progression.

Clinical features

• Patients may be asymptomatic.
• First manifestation is frequently syncope, sustained ventricular tachycardia, ventricular fibrillation or sudden death; arrhythmias occur particularly during emotional or physical stress.
• Palpitations and syncope.
• Atrial fibrillation and signs of right and/or left ventricular failure usually indicate advanced disease.

Histology

The characteristic finding is replacement of cardiomyocytes by fibrous and fatty tissue. Biopsy findings from the right ventricle are often non-specific because of patchy involvement; biopsy is therefore rarely performed.

Diagnosis

• Suspicion: particularly in young people with palpitations, cardiac syncope, documented ventricular tachyarrhythmias or survived unexplained cardiac arrest without evident structural heart disease.
• ECG: ventricular tachycardia with left bundle branch block morphology (right ventricular origin) and a superior axis – the axis helps to distinguish it from the usually benign idiopathic outflow tract tachycardia with an inferior axis; right precordial T-wave inversion, epsilon waves.
• Imaging: echocardiography, cardiac MRI, possibly cardiac CT or right ventricular angiography.
• Rhythm assessment: exercise testing, ambulatory ECG, electrophysiological study, signal-averaged ECG.
• Genetic testing: yield about 50–70 % when the diagnostic criteria are met; assessment of first-degree relatives.

Keep learning in the app

Further reading (open access)

1. MSD Manual Professional: Arrhythmogenic Right Ventricular Cardiomyopathy and Variants
2. StatPearls: Arrhythmogenic Right Ventricular Cardiomyopathy

Cross-references