BACKGROUND: Arrhythmogenic Right Ventricular Cardiomyopathy (ARVC) is a rare inherited cardiomyopathy currently diagnosed using established Task Force criteria consisting of ECHO, MRI, signal averaged ECG (SAECG), Holter monitoring, family history, and histologic tissue data. In early stages of disease, diagnosis is difficult, and these criteria may be insensitive. Anti-DSG2 is an antibody against a cadherin protein (DSG2) required in the formation of desmosomes which connect cardiac myocytes. It has been hypothesized that these antibodies arise from the exposure of novel epitopes to the immune system in the setting of mutations that disrupt the desmosome. It has been recently demonstrated that the anti-desmoglein-2 (Anti-DSG2) antibody is 100% sensitive in children and adults with clinical ARVC; it’s specificity is high in normal controls (0.97) as well as in small cohorts of hypertrophic and dilated cardiomyopathy; however, the specificity is not yet known in individuals with RV enlargement as a result of prolonged endurance exercise training, a well described form of cardiac remodelling. We tested for the presence of the Anti-DSG2 biomarker in a cohort of masters athletes with decades of athletic training.
METHODS AND RESULTS: In this prospective study, male and female athletes between the ages of 45-65 with a history of long-term endurance exercise training were recruited, and underwent cardiac MRI, Holter, and SAECG, and exercise history was collected. Athletes had RV enlargement but no ARVC on the basis of no major criteria for ARVC and no clinical characteristics of the disease by medical and family history. All athletes were healthy, and asymptomatic with no cardiac disease history. Participants were selected on the basis of RV enlargement which was defined as a RV end-diastolic volume indexed to Body Surface Area (RVEDVi) >100mL/m2 in women, and >110mL/m2 in men. Blood samples were collected and analyzed for the presence of the Anti-DSG2 antibody via western blot. Of 42 eligible participants, 30 consented to participate in this sub-study. Results are outlined in Table 1.
CONCLUSION: In a cohort of masters endurance athletes with RV enlargement but without ARVC, a novel biomarker used to detect ARVC was absent, suggesting that RV structural and electrical re-modelling in keeping with “athlete’s heart” is not associated with detectable anti-DSG2 antibodies. The absence of any false positive results implies that the anti-DSG2 antibody is highly specific for ARVC in this setting (specificity 100%; 95% CI, 88%-100%).