Exercise Restrictions for Carriers of the Mutation for Arrhythmogenic Right Ventricular Cardiomyopathy

For many years, there has been a sense by electrophysiologists that young patients who present with ventricular tachycardia or fibrillation (VT/VF), and are diagnosed with arrhythmogenic right ventricular cardiomyopathy/dysplasia (ARVD/C), always seem to be athletes. This sense is supported in the literature with clinical evidence that many patients with ARVD/C participate in endurance sports, and that athletes with ARVD/C are fivefold more likely to die of sudden death.¹ There is also experimental evidence that exercise training aggravates ARVD/C. In a clever study, plakoglobin-deficient mice were more likely to develop manifestations of the disease, including heart failure and ventricular arrhythmias, when they were subjected to intense swimming.² This relationship is plausible, given that ARVD/C is a disease of the structures that connect myocardial cells to one another, and that stress on the right ventricle is substantially higher during exercise than on the left ventricle. Based on these observations, patients with manifest ARVD/C are instructed to not participate in intense physical activity.

But what about the younger brother, or daughter, of the patient with ARVD/C, who is found to have the same genetic mutation? Should the mutation-positive relatives also be advised to avoid aerobic activity? To address this issue, the team at Johns Hopkins, led by Dr. Hugh Calkins, interviewed 87 desmosomal mutation-positive ARVD/C patients and their family members, who were identified using their ARVD/C Registry.³ Their findings consistently pointed toward a direct relationship between exercising and development of the phenotype.

For example, endurance athletes with desmosomal genetic mutations: 

• Developed symptoms at a younger age (30 vs. 41 years, p = 0.05);
• Were more likely to meet diagnostic criteria for ARVC/D (82% vs. 35%, p < 0.001), and;
• Were more likely to develop VT/VF and heart failure.

In addition, strikingly, among 61 individuals who did not present with VT/VF, all of the 13 subjects experiencing a first VT/VF event over a mean follow-up of 8 years were endurance athletes. 

Often the most challenging patients to counsel about physical activity restrictions are avid athletes. These patients are usually reluctant to stop participating in aerobic activities that have become a lifelong passion. This is especially the case when the data behind the recommendation is soft and/or based on opinion. Unfortunately, however, the evidence is mounting that not just patients with ARVC/D, but also those who are asymptomatic carriers of the mutation, should avoid participation in aerobic exercises and endurance training. 

References

1. Corrado D, Basso C, Rizzoli G, et al. Does sports activity enhance the risk of sudden death in adolescents and young adults? J Am Coll Cardiol. 2003;42:1959-1963.
2. Kirchhof P, Fabritz L, Zwiener M, et al. Age-and training-dependent development of arrhythmogenic right ventricular cardiomyopathy in heterozygous plakoglobin-deficient mice. Circulation. 2006;114:1799-1806.
3. James CA, Bhonsale A, Tichnell C, et al. Exercise increases age-related penetrance and arrhythmic risk in arrhythmogenic right ventricular dysplasia/cardiomyopathy-associated desmosomal mutation carriers. J Am Coll Cardiol. 2013;62:1290-1297.