Arrhythmogenic Right Ventricular Cardiomyopathy (ARVC)
Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a genetic disorder of the heart muscle. It is a rare inherited heart disease and an important cause of sudden death in young people and athletes¹. The disease accounts for 5–10% of sudden, unexplained deaths in people under 65 years of age².
In ARVC:
Fatty infiltration develops in the free wall of the right ventricle as a result of gene mutations.
A central feature of the disease is the development of ventricular tachycardia.
The risk of sudden death from ARVC has been estimated to be 5.4 times higher during competitive sport than with a sedentary lifestyle, and early identification of athletes with ARVC is essential for preventing sudden cardiac death during sport³.
Etiology
Arrhythmogenic right ventricular cardiomyopathy is typically inherited in an autosomal dominant pattern with variable penetrance and incomplete expression. Note: Penetrance describes the proportion of people with a specific gene mutation who develop signs and symptoms of the disease. If some carriers of the gene do not develop symptoms, this is referred to as reduced (or incomplete) penetrance⁴.
Approximately 40–50% of patients with ARVC have a mutation in genes encoding desmosomal proteins. Desmosomes are specialized connections between cells that help maintain the mechanical integrity of tissue.
The disease-causing gene is located on chromosome 14q23–q24.
Epidemiology
In the general population, the prevalence of ARVC is estimated to be between 1 in 2,500 and 1 in 5,000 people.
The prevalence is higher in Italy (Padua, Venice) and Greece (the island of Naxos).
The disease primarily affects young adults, with a male-to-female ratio of 2.7:1².
Signs and Symptoms of Arrhythmogenic Right Ventricular Cardiomyopathy
Arrhythmogenic cardiomyopathies may come to medical attention in different ways, but the earliest manifestation is most often symptomatic ventricular arrhythmia⁵. Presentation may range from an asymptomatic state to palpitations, fatigue, syncope or cardiac arrest during physical activity.
Diagnosis
Diagnosing arrhythmogenic right ventricular cardiomyopathy (ARVC/D) is challenging because no single test can establish the diagnosis on its own. Several diagnostic tools are required, including medical history, ECG, echocardiography, MRI and endomyocardial biopsy¹.
Pathophysiology
Arrhythmogenic right ventricular cardiomyopathy.jpeg
The pathogenesis of arrhythmogenic right ventricular cardiomyopathy/dysplasia (ARVC/D) remains unclear.
Genetic causes of ARVC involve at least eight different genes that affect cardiac muscle cells. Mutations in these genes affect desmosomes, structures that allow cardiac muscle cells to remain connected. When desmosomes fail, the cells lose their ability to remain attached, die and are replaced by scar tissue and fat. This stiffens the heart wall, particularly in the right ventricle, and can disrupt the electrical signals that regulate heart rhythm⁶.
Apoptosis appears to play an important role in disease development. The process begins in the subepicardial layers, spreads toward the endocardium and eventually produces transmural involvement. Aneurysmal dilatation occurs in approximately 50% of cases. ARVC/D is a progressive disease.
Treatment and Management
Implantable Cardioverter-Defibrillator (ICD)
The primary goal of treatment for ARVC/D is to prevent or reduce the risk of sudden cardiac death.
Management options include pharmacological treatment, surgical procedures, catheter ablation and implantation of an implantable cardioverter-defibrillator:
Pharmacological treatment: Aims to suppress arrhythmias and prevent thrombus formation.
Radiofrequency ablation: May be used to treat refractory or persistent ventricular tachycardia. Treatment has a success rate of 60–90%, but the progressive nature of the disease is associated with a recurrence rate of approximately 60%.
Implantable cardioverter-defibrillator (ICD): Is the most effective intervention for protection against sudden cardiac death.
Heart transplantation: May be necessary in patients with uncontrollable arrhythmias or right-sided or biventricular failure that cannot be managed with medical treatment¹.
Exercise and Physical Activity in Arrhythmogenic Right Ventricular Cardiomyopathy
More recent findings closely link arrhythmogenic right ventricular cardiomyopathy (ARVC) with physical activity and sports training. ARVC has long been recognized as an important cause of sudden cardiac death during physical activity, but it is now also recognized that intensive sports training can accelerate disease progression. In addition, there is evidence that excessive endurance training may produce an ARVC-like phenotype even in the absence of known genetic mutations associated with the disease.
Because high levels of physical activity are known to accelerate disease progression in ARVC and increase the risk of sudden cardiac death, it is essential that people with the diagnosis receive clear and precise advice about safe activity levels. Such advice should also be given to people who carry genetic mutations associated with ARVC even if they have not yet developed the disease.
Pragmatic Guidelines for Physical Activity in ARVC and Gene-Positive Carriers
Endurance training should be avoided completely.
Total exercise time should be limited to less than 2.5 hours per week.
High-intensity exercise should be avoided. Patients should be encouraged to exercise at an intensity well below their ventilatory threshold. A simple rule of thumb is that they should be able to hold a conversation during activity without becoming breathless.
Moderate static strength training may be acceptable⁵.
Sources:
Basso C, Corrado D, Marcus FI, Nava A, Thiene G. Arrhythmogenic right ventricular cardiomyopathy. The Lancet. 2009 Apr 11;373(9671):1289-300.: https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(09)60256-7/fulltext
Shah SN, Umapathi KK, Oliver TI. Arrhythmogenic right ventricular cardiomyopathy.https://www.statpearls.com/articlelibrary/viewarticle/17828/
Zorzi A, Corrado D. Arrhythmogenic Right Ventricular Cardiomyopathy. IOC Manual of Sports Cardiology. 2016 Nov 30:217-30.:https://onlinelibrary.wiley.com/doi/abs/10.1002/9781119046899.ch20
Medline Plus What are reduced penetrance and variable expressivity? from:https://medlineplus.gov/genetics/understanding/inheritance/penetranceexpressivity/
Prior D, La Gerche A. Exercise and arrhythmogenic right ventricular cardiomyopathy. Heart, Lung and Circulation. 2020 Apr 1;29(4):547-55.from:https://www.sads.org/SADS/media/Literature-Review/Exercise-and-Arrhythmogenic-Right-Ventricular-Car_2020_Heart--Lung-and-Circu.pdf
Genetic ed Fact Sheet 57| CARDIOMYOPATHIEShttps://www.genetics.edu.au/publications-and-resources/facts-sheets/fact-sheet-57-cardiomyopathies
