Arrhythmogenic Right Ventricular Cardiomyopathy
Introduction[edit | edit source]
Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a genetic disorder of the myocardium (heart muscle). It is is a rare inherited heart-muscle disease that is a cause of sudden death in young people and athletes. This disorder accounts for 5% to 10% of sudden unexplained death in individuals less than 65 years of age.
- Due to fatty infiltration of the right ventricular free wall, this results from the mutation of genes.
- An essential feature of this disease is the development of ventricular tachycardia.
- The risk of dying suddenly from ARVC has been estimated to be 5.4 times greater during competitive sports than during sedentary activity, and early identification of athletes with ARVC plays a crucial role in the prevention of sudden cardiac death during sport.
Etiology[edit | edit source]
Arrhythmogenic right ventricular cardiomyopathy is typically inherited as an autosomal dominant pattern with variable penetrance and incomplete expression NB Penetrance refers to the proportion of people with a particular gene mutation who exhibit signs and symptoms of a genetic disorder. If some people with the variant do not develop features of the disorder, the condition is said to have reduced (or incomplete) penetrance. 
- Approximately 40% to 50% of ARVC/D patients have a mutation in genes encoding a desmosome protein (specialized adhesive protein complexes that localize to intercellular junctions and are responsible for maintaining the mechanical integrity of tissues)
- The gene is on the chromosome 14q23-q24.
Epidemiology[edit | edit source]
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.
Exercise Prescription in ARVC[edit | edit source]
A recent finding with ARVC is the important interaction of this condition with exercise and athletic training. It has long been known that ARVC is an important cause of sudden cardiac death with exercise , but more recently it has been recognised that athletic training can accelerate the progression of the disease and also that excessive endurance exercise may be a cause of an ARVC-like phenotype, even in the absence of genetic abnormalities known to be associated with ARVC.
Because high level exercise is known to accelerate the progression of ARVC and increase the risk of sudden death, individuals with the diagnosis need clear advice about how much exercise is safe. It is wise to provide advice both to those with a definite diagnosis of ARVC and to those who carry a mutation known to cause ARVC
Pragmatic exercise advice in ARVC and in gene positive carriers.
- 1. Endurance exercise should be avoided.
- 2. Exercise should be limited to less than 2.5 hours per week
- 3. Intense exercise should be avoided. Patients should be encouraged to exercise well below ventilatory threshold. Simple guidance like exercising at a level where you can maintain conversation may be useful.
- 4. Moderate static strength-based exercise may be reasonable.
Signs and Symptoms[edit | edit source]
Arrhythmogenic cardiomyopathies may come to medical attention in a variety of ways but the earliest manifestation is most frequently with symptomatic ventricular arrhythmias. However presentation varies from the asymptomatic state to palpitations, fatigue, syncope, or cardiac arrest during exercise.
Diagnosis[edit | edit source]
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.
Pathophysiology[edit | edit source]
Arrhythmogenic right ventricular cardiomyopathy/dysplasia pathogenesis is unknown.
Genetic causes of ARVC include at least eight genes which are involved once again in heart muscle cells.
- Mutations in ARVC genes affect desmosomes which are structures that allow one heart muscle cell to communicate with the cell next to it. When desmosomes don’t work properly cells disconnect and die off, being replaced by scar tissue and fat. This stiffens the heart wall, particularly in the right ventricle, and may interrupt electrical signals that control regular heart rhythm.
- 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.
- ARVC/D is a progressive disease.
Image: Arrhythmogenic_right_ventricular_cardiomyopathy. In vitro MRI (c) and corresponding cross section of the heart (d) show RV dilatation with anterior and posterior aneurysms.
Treatment / Management[edit | edit source]
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.
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
References[edit | edit source]
- Basso C, Corrado D, Marcus FI, Nava A, Thiene G. Arrhythmogenic right ventricular cardiomyopathy. The Lancet. 2009 Apr 11;373(9671):1289-300.Available: https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(09)60256-7/fulltext(accessed 26.4.2021)
- Shah SN, Umapathi KK, Oliver TI. Arrhythmogenic right ventricular cardiomyopathy.Available from: https://www.statpearls.com/articlelibrary/viewarticle/17828/(accessed 26.4.2021)
- Zorzi A, Corrado D. Arrhythmogenic Right Ventricular Cardiomyopathy. IOC Manual of Sports Cardiology. 2016 Nov 30:217-30.Available:https://onlinelibrary.wiley.com/doi/abs/10.1002/9781119046899.ch20 (accessed 26.4.2021)
- Medline Plus What are reduced penetrance and variable expressivity? Available from:https://medlineplus.gov/genetics/understanding/inheritance/penetranceexpressivity/ (accessed 26.4.2021)
- Prior D, La Gerche A. Exercise and arrhythmogenic right ventricular cardiomyopathy. Heart, Lung and Circulation. 2020 Apr 1;29(4):547-55.Available from:https://www.sads.org/SADS/media/Literature-Review/Exercise-and-Arrhythmogenic-Right-Ventricular-Car_2020_Heart--Lung-and-Circu.pdf (accessed 26.4.2021)
- Genetic ed Fact Sheet 57| CARDIOMYOPATHIEShttps://www.genetics.edu.au/publications-and-resources/facts-sheets/fact-sheet-57-cardiomyopathies (accessed 26.4.2021)