Arrhythmogenic right ventricular cardiomyopathy (ARVC), also called arrhythmogenic right ventricular dysplasia (ARVD), is a genetic cardiac disorder affecting mainly the right ventricle and causing ventricular tachyarrhythmias and increased risk of sudden death. Symptoms include palpitations, syncope, and cardiac arrest, and with worsening disease, manifestations of right ventricular failure. Diagnosis includes ECG, cardiac imaging, and consensus criteria. Treatment requires limitation of physical exertion and usually a beta-blocker and an implantable cardioverter-defibrillator (ICD).
(See also Overview of Arrhythmogenic Cardiomyopathies and Overview of Arrhythmias.)
A number of genetic mutations adversely affect the structure and function of the intercalated disk, the structure that connects cardiac myocytes. Most commonly, the mutations affect the component of the disk known as the desmosome (the adhesive intercellular junction that tethers intermediate filaments to cell membranes). Desmosomes help connect cells in tissues that undergo mechanical stress, such as cardiac myocytes. The desmosomal proteins that may be affected include plakophilin, desmoplakin, and desmoglein. When abnormal, these proteins are prone to damage by mechanical stress (eg, from increased cardiac workload as from prolonged exertion). Healing of the damage leads to replacement of myocytes by fibrofatty tissue, predominantly in the triangle between the right ventricular outflow tract, the right ventricular inflow tract, and the right ventricular apex, but sometimes also involving the posterolateral left ventricle, predominantly or exclusively. Disease manifestations are the result of both electrophysiologic and structural changes, initially manifesting as ventricular premature beats and ventricular tachyarrhythmias but eventually causing right ventricular structural abnormalities (eg, dilation and thinning), resulting in congestive right ventricular cardiomyopathy. A left ventricular cardiomyopathy may also occur with biventricular or predominantly left ventricular disease.
Most commonly, the mutations are inherited with an autosomal dominant pattern with variable penetrance; however, autosomal recessive mutations are known. The incidence of ARVC has regional variation from 1 in 2000 to 1 in 5000 (1). It is thought that sustained, heavy exertion (eg, from endurance athletics) hastens onset and progression of disease.
General reference
1. Krahn AD, Wilde AAM, Calkins H, et al. Arrhythmogenic Right Ventricular Cardiomyopathy. JACC Clin Electrophysiol 2022;8(4):533-553. doi:10.1016/j.jacep.2021.12.002
Symptoms and signs of ARVC
Patients may be asymptomatic, but those who are symptomatic usually present first with ventricular tachycardia (VT), ventricular fibrillation (VF), or sudden death. ARVC is responsible for approximately 10% of sudden deaths in young adults (1). Ventricular tachyarrhythmias are particularly likely to occur during emotional or physical stress.
Patients may have palpitations or syncope,
Atrial fibrillation and signs of right and/or left ventricular systolic failure are usually manifestations of advanced disease.
Symptoms and signs reference
1. Krahn AD, Wilde AAM, Calkins H, et al. Arrhythmogenic Right Ventricular Cardiomyopathy. JACC Clin Electrophysiol 2022;8(4):533-553. doi:10.1016/j.jacep.2021.12.002
Diagnosis of ARVC
ECG
Sometimes signal-averaged ECG
Cardiac imaging (eg, echocardiography, cardiac magnetic resonance imaging, right ventricular angiography)
Sometimes right ventricular biopsy
Genetic testing
Screening of first-degree family members
Diagnosis of ARVC is difficult in the absence of advanced right ventricular systolic dysfunction, leading to historic under-recognition of the disorder. ARVC should be suspected in patients, particularly young patients, with palpitations, cardiac syncope, documented ventricular tachyarrhythmias, or resuscitation from unexplained cardiac arrest in the absence of clinically evident structural heart disease.
The diagnosis of ARVC is often first suspected when it is recognized that the patient's ventricular arrhythmias are of right ventricular origin, typically indicated by a left bundle branch block–shaped QRS complex with a superior frontal plane axis (the latter helping to differentiate ARVC from the more benign idiopathic right ventricular outflow tract ventricular tachycardia, which usually has an inferior frontal plane QRS axis).
The initial evaluation of patients with suspected arrhythmogenic cardiomyopathy includes history, family history, ECG, 2-dimensional echocardiography, and cardiac MRI. If no spontaneous ventricular arrhythmia has been demonstrated, exercise testing, ambulatory ECG monitoring, and/or electrophysiologic testing may be required. If the diagnosis remains in doubt, other testing may include signal averaged ECG, electrophysiologic testing, and right ventricular endomyocardial biopsy (1). Right ventricular angiography is not routine but, if done, may reveal characteristic structural abnormalities and also allow biopsy of the right ventricle; however, biopsy findings are often nonspecific and biopsy is rarely done.
Because no single test is diagnostic, major and minor diagnostic criteria have been proposed by an international task force (2). The criteria include
Evidence of right ventricular disease on imaging studies
Right ventricular biopsy showing replacement of myocytes by fibrous tissue, fatty tissue, or both
ECG repolarization changes including right precordial T-wave inversion
ECG depolarization changes including right precordial epsilon waves
Signal-averaged ECG showing late potentials
Documented ventricular arrhythmias originating from the right ventricle
Family history of ARVC or sudden death
Identification of a gene mutation associated with ARVC
The key entities to consider in the differential diagnosis are cardiac sarcoidosis, athlete's heart, myocarditis, and idiopathic right ventricular outflow tract VT.
Genetic testing is usually done in patients suspected of having ARVC. The yield of testing is about 50% when task force criteria are met (3).
First-degree family members of patients have a significant risk of disease. Starting at age 10 to 12 years and every 1 to 3 years thereafter, they should have clinical evaluation (ie, to detect symptoms suggestive of arrhythmia), ECG, ambulatory ECG monitoring, and echocardiography. Genetic testing is done if the index case has a mutation identified. Family members without the index mutation are then freed of follow-up investigations.
Diagnosis references
1. Towbin JA, McKenna WJ, Abrams DJ, et al: 2019 HRS expert consensus statement on evaluation, risk stratification, and management of arrhythmogenic cardiomyopathy. Heart Rhythm 16(11):e301–e372, 2019. doi:10.1016/j.hrthm.2019.05.007
2. Corrado D, Anastasakis A, Basso C, et al: Proposed diagnostic criteria for arrhythmogenic cardiomyopathy: European Task Force consensus report. Int J Cardiol 395:131447, 2024. doi:10.1016/j.ijcard.2023.131447
3. Ackerman MJ, Priori SG, Willems S, et al: HRS/EHRA expert consensus statement on the state of genetic testing for the channelopathies and cardiomyopathies this document was developed as a partnership between the Heart Rhythm Society (HRS) and the European Heart Rhythm Association (EHRA). Heart Rhythm 8(8):1308–1339, 2011. doi:10.1016/j.hrthm.2011.05.020
Treatment of ARVC
Moderation of physical activity
Often an implantable cardioverter-defibrillator (ICD)
Usually a beta-blocker
Heart failure therapy (including transplantation) as required
Treatment of ARVC focuses on prevention of sudden death and prevention of symptomatic ventricular tachyarrhythmias.
Patients should avoid endurance athletics because such activities foster both disease progression and occurrence of life-threatening arrhythmias. These risks are higher in males and in patients with more advanced disease (as evidenced by more task force criteria) (1).
The 5-year risk of a first episode of life-threatening arrhythmia ranges from approximately 2% to 50%, depending on age, sex, cardiac syncope within 1 year of diagnosis, non-sustained VT, ventricular premature beat frequency, the extent of T-wave inversion, and the RV ejection fraction. An online risk calculator for patients who have not yet had a life-threatening arrhythmia is available (https://www.ARVCrisk.com).
Prevention of sudden death is by an ICD (see also table Indications for an ICD). An ICD is recommended for patients with ARVC and the following (1):
Resuscitated cardiac arrest
Prior sustained VT with hemodynamic instability
Severe right ventricular (or left ventricular) systolic dysfunction
Possibly prior sustained VT without hemodynamic instability (class IIa indication])
Possibly syncope suspected to be due to ventricular arrhythmia (class IIa indication)
Possibly various combinations of major and minor risk factors for ventricular arrhythmia (class IIa and class IIb indications)
Significant right or left ventricular dysfunction will require medical therapy. A beta-blocker should be used in most patients.
Treatment reference
1. Towbin, JA, McKenna WJ, Abrams DJ, et al: 2019 HRS expert consensus statement on evaluation, risk stratification, and management of arrhythmogenic cardiomyopathy. Heart Rhythm 16:e301–e372, 2019. doi: 10.1016/j.hrthm.2019.05.007
Key Points
Arrhythmogenic right ventricular cardiomyopathy is a genetic disorder in which myocytes are replaced by fibrofatty tissue, leading to arrhythmias and later right ventricular failure.
The disorder progresses quicker in patients who engage in endurance exercise.
Diagnosis is based on consensus criteria involving clinical and electrocardiographic factors, cardiac imaging, and genetic testing.
First-degree family members have a significant risk of disease and require initial screening and regular testing.
Treatment requires moderation of physical activity, beta-blockade, and often an ICD.
