Arrhythmogenic right ventricular cardiomyopathy (ARVC), a condition also known as arrhythmogenic right ventricular dysplasia (ARVD), is a genetic disorder of the myocardium. ARVC/D is due to fatty infiltration of the right ventricular free wall. This results from the mutation of genes and can cause sudden death in young people and athletes. It was first identified in 1977 by Guy Fontaine. An essential feature of this disease is the development of ventricular tachycardia with left bundle branch block pattern. It commonly presents during exercise. Identification of this disease can prevent death in patients with the disease by doing preventive measures. Genetic testing is essential in their family members to identify at-risk individuals.
Arrhythmogenic right ventricular cardiomyopathy is typically inherited as an autosomal dominant pattern with variable penetrance and incomplete expression. Approximately 40% to 50% of ARVC/D patients have a mutation in genes encoding a desmosome protein. The gene is on the chromosome 14q23-q24.There is an autosomal recessive trait variant associated with palmoplantar keratosis and wooly hair named Naxos disease.
In the general population, the prevalence of ARVC/D is 1 per 2500 to 1 per 5000. The prevalence is higher in Italy (Padua, Venice) and Greece (Island of Naxos). This disorder accounts for 5% to 10% of sudden unexplained death in individuals less than 65 years of age. It occurs in young adults and has a male to female ratio of 2.7 to 1.
Arrhythmogenic right ventricular cardiomyopathy/dysplasia pathogenesis is unknown. Apoptosis seems to play a role in pathogenesis. The disease process initiates in the subepicardial region, extends to the endocardial surface, and leads to transmural involvement.
Aneurysmal dilatation is present in 50% of the cases. An aneurysm occurs in the diaphragm, apical area, and infundibulum, known as the triangle of dysplasia. The left ventricle is involved in 50% to 67% of cases. Involvement of the left ventricle suggests a poor prognosis. The two pathology patterns seen with ARVC/D are fatty infiltration and fibro-fatty infiltration.
ARVC/D is a progressive disease. The right ventricle becomes more involved over time, leading to right ventricular failure. By the time the individual develops right ventricular failure, the left ventricle may develop histologic changes. Eventually, the left ventricle failure develops, leading to biventricular failure. The disease further progresses to congestive heart failure, atrial fibrillation, and thromboembolic events.
Microscopic features of the right ventricle show several changes of which the dominant feature is the presence of fibrofatty or fat replacement of the myocardial muscle. The muscles may show a moth-eaten appearance, mild inflammation, and scarring. Very rarely does one see frank myocyte necrosis. Some researchers are using immunohistochemistry to reveal the diffuse loss of desmosomal proteins, which is suggestive of an arrhythmogenic right ventricle.
Arrhythmogenic right ventricular cardiomyopathy/dysplasia presentation varies from the asymptomatic state to palpitations, fatigue, syncope, or even cardiac arrest during exercise. Sometimes one will see prominence in the left side of the heart due to enlargement of the right Ventricle. Other than this, the physical exam is usually unremarkable.
Diagnosis of ARVC/D is challenging. No one test can make the diagnosis, and multiple diagnostic tools are utilized including history, ECG, echo, MRI, and endomyocardial biopsy.
The diagnosis of ARVC/D is based on a combination of major and minor criteria. Diagnosis of ARVC/D requires two major criteria or one major and two minor criteria or four minor criteria.
Right ventricular dysfunction
Right ventricular dysfunction
The goal of ARBC/D management is to prevent or decrease sudden cardiac death.
Management of ARVC/D includes pharmacologic, surgical, catheter ablation, and placement of implantable cardiac defibrillator.
1. Pharmacologic treatment involves arrhythmia suppression and prevention of thrombus formation.
2. Radiofrequency catheter ablation may be used to treat refractory or incessant ventricular tachycardia. It is 60 to 90% successful. Recurrence rate is 60% due to the progression of the disease.
3. The implantable cardiac defibrillator is the most effective against sudden cardiac death. Indications for ICD in ARVC/D are:
4. Cardiac transplant surgery is performed in ARVC/D if there is uncontrolled arrhythmia or failure to manage right ventricular or biventricular failure with pharmacologic therapy.
At autopsy, one has to differentiate between normal fat deposition in the right ventricle and the presence of scars in the subepicardium due to ischemia. In most hearts, some amount of adipose tissue is present in the right ventricle, but there are usually no myocyte changes or presence of fibrosis.
In the past the prognosis was poor, but with the availability of cardiac MRI and CT tomography, the diagnosis is made much earlier. The screening of young athletes also has saved lives. Today, the long-term prognosis is favorable, especially in family members who undergo screening for the disorder.
All first-degree family members should receive screening for ARVC/D. Screening including ECG, echocardiogram, signal-averaged ECG, Holter monitor, cardiac MRI, and exercise stress test should begin during the teenage years.
Since this disease is genetically transmitted, clinicians should encourage other family members to have screening done. Once the disease has been diagnosed, the patient needs life long follow up. Because of the varied treatments available, a multidisciplinary team must be involved in decision making. While the lifespan has increased with treatment, sudden death still does occur in patients who are undertreated or undiagnosed.