Exercise restriction is protective for genotype-positive family members of arrhythmogenic right ventricular cardiomyopathy patients

Abstract

Aims In arrhythmogenic right ventricular cardiomyopathy (ARVC) patients, exercise worsens disease course, so exercise restriction is recommended. However, recommendations for genotype-positive ARVC family members is incompletely resolved. We aimed to provide evidence for exercise recommendations for genotype-positive ARVC family members. Methods and results Arrhythmogenic right ventricular cardiomyopathy family members inheriting a pathogenic desmosomal variant were interviewed about exercise history from age 10. Exercise was characterized by duration, intensity, and dose (duration*intensity). Associations between exercise and (i) diagnosis by 2010 Task Force Criteria and (ii) development of sustained ventricular arrhythmias were examined. The study included 101 family members (age: 40.5 ± 19.3 years, male: 41%, Plakophilin-2 variant: 81%). Forty-four individuals (44%) met diagnostic criteria and 16 (16%) experienced sustained ventricular arrhythmia. Individuals who met diagnostic criteria had significantly higher average exercise duration and dose, but not peak intensity than those who did not. Only one individual who exercised below the American Heart Association recommended minimum (650 metabolic equivalent of task-hours/year) met diagnostic criteria or experienced sustained ventricular arrhythmia as opposed to 50% of individuals who exceeded it (adjusted odds ratio = 0.03, 95% confidence interval 0.003–0.26). The difference in exercise exposure between affected and unaffected individuals was more striking in females than in males. Females who had done high-dose exercise in adolescence had the worst survival free from diagnosis (P < 0.01). Conclusions In phenotype-negative ARVC family members with a pathogenic desmosomal variant, athletic activities should be limited, particularly exercise dose. Exercise may play a greater role in promoting disease in female family members.

Sex differences in disease progression and arrhythmic risk in patients with arrhythmogenic cardiomyopathy

“…This is in line with a recent study reporting a strong association between exercise dose and definite AC criteria and VA in mutation-positive family members, and this association was more prominent in females. 17 …”

“…Exercise dose was also assessed dichotomized as below or above 12.5 MET h/week, based on the American Heart Association/American College of Sports Medicine recommendations 16 and a recent publication on exercise restriction in genotype-positive AC family members. 17 High-intensity exercise was defined as >6 METs. 16 Athletes were defined as exercise doses equivalent to ≥4 h of high-intensity exercise per week according to a previously used definition of athletic activity.…”

International Evidence Based Reappraisal of Genes Associated With Arrhythmogenic Right Ventricular Cardiomyopathy Using the Clinical Genome Resource Framework

“… 47 Among relatives of patients with ARVC with P/LP desmosomal variants, exercise increases penetrance and risk of incident arrhythmias, but not all athletic relatives develop ARVC. 48 . Additionally, a recent study 49 showed 0.23% of a general clinical population harbored a loss of function desmosomal variant.…”

Insights Into Genetics and Pathophysiology of Arrhythmogenic Cardiomyopathy

“…Management strategies focus on symptom relief, slowing disease progression and prevention of arrhythmias and SCD [ 11 ]. In addition, lifestyle interventions and in particular exercise restriction are recommended [ 12 ]. Exercise is an important risk factor.…”