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. 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.
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. It is thought that sustained, heavy exertion (eg, from endurance athletics) hastens onset and progression of disease.
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. Ventricular tachyarrhythmias are particularly likely to occur during emotional or physical stress. Atrial fibrillation and signs of right ventricular systolic failure (eg, dependent edema, ascites) are usually manifestations of advanced disease.
Diagnosis of ARVC
ECG and 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 arrhythmogenic right ventricular cardiomyopathy is difficult in the absence of advanced right ventricular systolic dysfunction, leading to historic under-recognition of the disorder. ARVC should be suspected particularly in 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). Patients should have ECG, signal-averaged ECG, echocardiography, and cardiac MRI. If no spontaneous ventricular arrhythmia has been demonstrated, exercise testing, ambulatory ECG monitoring, and/or electrophysiologic testing may be required. 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.
Because no single test is diagnostic, major and minor diagnostic criteria have been proposed by an international task force (1). 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
Genetic testing is usually done in patients suspected of having ARVC. The yield of testing is about 60% when task force criteria are met.
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 reference
1. Marcus FI, McKenna WJ, Sherrill D, et al: Diagnosis of arrhythmogenic right ventricular cardiomyopathy/dysplasia: proposed modification of the task force criteria. Eur Heart J 31;806–814, 2010. doi: 10.1093/eurheartj/ehq025
Treatment of ARVC
Moderation of physical activity
Often an ICD
Usually a beta-blocker
Heart failure therapy (including transplantation) as required
Treatment of arrhythmogenic right ventricular cardiomyopathy 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 men and in patients with more advanced disease (as evidenced by more task force criteria).
Prevention of sudden death is by an ICD (see also table Indications for an ICD). An ICD is recommended for patients with prior sustained VT or resuscitated cardiac arrest or severe right ventricular (or left ventricular) systolic dysfunction. An ICD also may be useful for patients with any major risk factor for sudden death, including prior syncope, non-sustained ventricular tachycardia, or moderate right or left ventricular systolic dysfunction (class IIa indication). A recent Heart Rhythm Society consensus statement also provided recommendations regarding ICD use in patients with ARVC and various combinations of moderate other risk factors (1).
Antiarrhythmic therapy with a class III drug
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.
