Arrhythmogenic right ventricular cardiomyopathy

Formerly called arrhythmogenic right ventricular dysplasia.

What is arrhythmogenic right ventricular cardiomyopathy?

Arrhythmogenic right ventricular cardiomyopathy (ARVC) is caused by fibro-fatty replacement of RV myocytes due to apoptosis, inflammation (definite causes for either mechanism are as yet unknown) or a genetic cause. It usually presents with symptomatic arrhythmias or sudden death.

Diagnosing ARVC is difficult due to nonspecific disease features and phenotypic manifestations. Echocardiographic features include increased RV dimensions, RV regional wall motion abnormalities and dysfunction. RV angiography has been considered the gold standard for diagnosis, but MRI has better sensitivity and specificity.

In ARVC, severe RV dysfunction is treated with standard heart failure medications and cardiac transplantation is considered if treatment is refractory. Beta-blockers are used in asymptomatic patients and implantable cardioverter defibrillator (ICD) is mandated in high-risk patients.

The precise aetiology remains unknown.

There are separate articles which discuss Cardiomyopathies, Hypertrophic Cardiomyopathy and Dilated Cardiomyopathies.

How common is arrhythmogenic right ventricular cardiomyopathy? (Epidemiology)

• ARVC is uncommon, affecting between 1 in 2,000 - 1 in 5,000 adults.¹ It is more common in people from northern Italy and Greece.

• ARVC most often presents in adolescence and early adulthood.

• It is more common in males.

• It is familial in 30-50%of cases.

• It is transmitted in autosomal dominant (more common) and autosomal recessive forms and involves mutations in desmosomal and extra-desmosomal genes.²

• ARVC is recognised as a leading cause of sudden cardiac death (SCD) in young adults under 35 years of age and may even account for up to 10% of cardiovascular deaths in the under-65 age group.³

Symptoms of arrhythmogenic right ventricular cardiomyopathy (presentation)

ARVC generally presents in men aged 15-35 with palpitations, presyncope or syncope. Sudden death can be the first presentation. Patients who survive into their fourth and fifth decades can present with biventricular or right heart failure (without pulmonary hypertension).

Atrial arrhythmias are common in ARVC and present at a younger age than in the general population. They are associated with male gender, increasing age, and left atrial enlargement. Atrial arrhythmias are clinically important, as they are associated with inappropriate ICD shocks and increased risk of both death and heart failure.⁴

The features of ARVC depend on the phase of disease progression:

• Concealed phase:

  • Subtle RV changes, with or without minor ventricular arrhythmias.

  • These may occasionally be the first manifestation as SCD, usually in the young engaged in competitive sports or intense exercise.

• Overt electrical disorder:

  • Symptomatic RV arrhythmias associated with functional and structural abnormalities of the right ventricle.

  • Usually presents with palpitations or syncope.

  • Arrhythmias and SCD are common. Previously undiagnosed ARVC accounts for about 20% of SCDs.

• Right ventricular (RV) failure:

  • Extension of disease to the whole of the right ventricle causes dysfunction.

• Biventricular pump failure - end stage:

  • Left ventricular involvement leads to heart failure and may mimic dilated cardiomyopathy.

NB: around half of patients will have a normal physical examination.

Diagnosing arrhythmogenic right ventricular cardiomyopathy (investigations)

The following investigations are usually undertaken:

• Assessment of cardiac function and disease aetiology:

  • Blood tests, including FBC, ESR/CRP, renal function and electrolytes, and LFTs; cardiac enzymes may be appropriate, depending on presentation.

  • ECG - the most common findings are ventricular arrhythmias with left bundle branch block (LBBB) morphology.

  • CXR.

  • Echocardiogram.

  • Cardiac catheterisation.

  • Cardiac MRI scan - RV enlargement, fatty infiltration, fibrosis and wall motion abnormalities.

  • RV angiography is considered a very useful test to diagnose classic forms of ARVC and to evaluate RV function.

  • Heart biopsy in some cases.

• Genetic assessment.

  • Offer screening to first degree relatives of confirmed cases.⁵

Management of arrhythmogenic right ventricular cardiomyopathy

Medication

For patients with well tolerated, or non life-threatening ventricular arrhythmias, beta-blockers, such as sotalol, or amiodarone with/without beta-blocker, are the most effective drugs with a relatively low proarrhythmic risk.
For sustained ventricular tachycardia (VT) or ventricular fibrillation (VF), serial therapeutic drug trials are used, using programmed ventricular stimulation to assess effectiveness. Treat associated heart failure which may develop in 50% of patients.¹

Surgical

Radio-frequency ablation results in a significant reduction in the burden of VT in patients with ARVC.⁶

• Patients who remain inducible of arrhythmias usually require an ICD, except for rare cases with localised disease where catheter ablation may be an option.

• In patients who are not inducible, and present in cardiac arrest or syncope, an automatic ICD is the first option.

• ICDs are the most effective intervention in prevention of arrhythmic sudden cardiac death (SCD). ⁷

• Cardiac and non-cardiac mortality rates after ICD implantation in patients with ARVC are low.⁸ SCD occurs in 0.65 per 1000 patients per year who have an ICD and in 7.2 per 1000 of those without an ICD.⁹

• Those who show ventricular arrhythmia despite medication and ICD implantation may require epicardial ablation.¹

• Heart transplantation may need to be considered for refractory cases in end-stage failure.

Prognosis

The availability of cardiac MRI and CT has facilitated earlier diagnosis and allowed screening for family members and young athletes.⁵ As a result the prognosis has improved.

• ARVC tends to be progressive with deterioration of RV function.

• The left ventricle may become involved with progression of the degenerative process.

• Although AVRC is a progressive disease, the individual disease course can vary considerably.

• The mortality rate is currently estimated to be around 1-3% per year.³