Continuing Education Activity

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. This activity reviews the presentation of arrhythmogenic right ventricular cardiomyopathy and highlights the role of the interprofessional team in its management.

Objectives:

• Describe the pathophysiology of arrhythmogenic right ventricular cardiomyopathy (ARVC).
• Review the clinical presentation of a patient with arrhythmogenic right ventricular cardiomyopathy (ARVC).
• Outline the treatment and management options available for arrhythmogenic right ventricular cardiomyopathy (ARVC).
• Explain the importance of improving care coordination among interprofessional team members to improve outcomes for patients affected by arrhythmogenic right ventricular cardiomyopathy (ARVC).

Introduction

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.[1] 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.[2] 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.

Etiology

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.[3]There is an autosomal recessive trait variant associated with palmoplantar keratosis and wooly hair named Naxos disease.[4]

Epidemiology

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.

Pathophysiology

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.

Histopathology

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.

History and Physical

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.

Evaluation

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.

• ECG - The most common ECG abnormality seen in ARVC/D is T wave inversion in the precordial leads V1 to V3.[5] The epsilon wave is found in 50% of cases of ARVC/D. These are due to post excitation electrical impulses of small amplitude, and they tend to occur at the end of QRS complexes and during the beginning of ST segment; this is due to delayed right ventricular activation.[6] Ventricular ectopy of left bundle branch block morphology with QRS axis -90 to +100 degree is from fatty degeneration of right ventricle (RV apex, RV inflow tract, RV outflow tract).

• Echocardiography - Echocardiography may reveal an enlarged right ventricle (RV), hypokinetic RV, and paper thin RV free wall.

• Cardiac MRI - Cardiac MRI is an excellent tool for visualizing the right ventricle. It may reveal a transmural diffuse bright signal in the RV free wall due to myocardial atrophy with fatty replacement.

• Endomyocardial biopsy - Transvenous biopsy of the right ventricle can be highly specific for ARVC/D, but it has low sensitivity.

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.[7]

Major Criteria

Right ventricular dysfunction

• Severe dilatation and accompanying reduction of RV ejection fraction with minimal or no LV impairment
• Localized RV aneurysms
• Severe segmental dilatation of the RV

Tissue characterization

• Fibrofatty replacement of myocardium on endomyocardial biopsy

Conduction abnormalities

• Epsilon waves in V1 - V3
• Localized prolongation (greater than 110 ms) of QRS in V1-V3

Family history

• Familial disease confirmed on autopsy or surgery

Minor Criteria

Right ventricular dysfunction

• Mild global right ventricular dilatation and/or reduced ejection fraction with a normal left ventricle
• Mild segmental dilatation of the right ventricle
• Regional RV hypokinesis

Tissue characterization

Conduction abnormalities

• Inverted T waves in V2 and V3 in a patient over 12 years old, in the absence of right bundle branch block
• Late potentials on signal-averaged ECG
• Ventricular tachycardia accompanied by left bundle branch block morphology
• Frequent PVCs (greater than 1000 PVCs per 24 hours)

Family history

• A family history of sudden cardiac before age 35
• A family history of ARVC/D

Treatment / Management

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.

• Sotalol is a beta blocker and class III antiarrhythmic agent. It is the most effective antiarrhythmic agent in ARVC/D.[8]
• Warfarin is an anticoagulant. With decreased right ventricular ejection fraction and dyskinesis, anticoagulation may help prevent thrombus formation and further complications such as pulmonary embolism.

2. Radiofrequency catheter ablation may be used to treat refractory or incessant ventricular tachycardia.[9] 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.[10] Indications for ICD in ARVC/D are:

• Cardiac arrest secondary to ventricular tachycardia or ventricular fibrillation
• Symptomatic ventricular tachycardia that is not inducible during programmed stimulation
• Failed programmed stimulation-guided drug therapy
• Severe right ventricular involvement with poor tolerance of ventricular tachycardia
• The sudden death of an immediate family member

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.[11]

Differential Diagnosis

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.

Prognosis

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.

Complications

Arrhythmias including sudden death

Heart failure

Consultations

• Cardiologist
• Electrophysiologist
• Genetics

Pearls and Other Issues

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.

Enhancing Healthcare Team Outcomes

Since arrhythmogenic right ventricular cardiomyopathy 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, an interprofessional 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.