Abstract
BACKGROUND: The arrhythmogenic right ventricular cardiomyopathy (ARVC) risk calculator stratifies risk for incident sustained ventricular arrhythmias (VA) at the time of ARVC diagnosis. However, included risk factors change over time, and how well the ARVC risk calculator performs at follow-up is unknown. METHODS: This was a retrospective analysis of patients with definite ARVC and without prior sustained VA. Risk factors for VA including age, nonsustained ventricular tachycardia, premature ventricular complex burden, T-wave inversions on electrocardiogram, cardiac syncope, right ventricular function, therapeutic medication use, and exercise intensity were assessed at the time of 2010 Task Force Criteria based ARVC diagnosis and upon repeat evaluations. Changes in these risk factors were analyzed over 5-year follow-up. The 5-year risk of VA was predicted longitudinally using (1) the baseline ARVC risk calculator prediction, (2) the ARVC risk prediction calculated using updated risk factors, and (3) time-varying Cox regression. Discrimination and calibration were assessed in comparison to observed VA event rates. RESULTS: Four hundred eight patients with ARVC experiencing 132 primary VA events were included. Matched comparison of risk factors at baseline versus at 5 years of follow-up revealed decreased burdens of premature ventricular complexes (-1200/day) and nonsustained ventricular tachycardia (-14%). Presence of significant right ventricular dysfunction and number of T-wave inversions on electrocardiogram were unchanged. Observed risk for VA decreased by 13% by 5 years follow-up. The baseline ARVC risk calculator's ability to predict 5-year VA risk worsened during follow-up (C statistics, 0.83 at diagnosis versus 0.68 at 5 years). Both the updated ARVC risk calculator (C statistics of 0.77) and time-varying Cox regression model (C statistics, 0.77) had strong discrimination. The updated ARVC risk calculator overestimated 5-year VA risk by an average of +6%. CONCLUSIONS: Risk factors for VA in ARVC are dynamic, and overall risk for incident sustained VA decreases during follow-up. Up-to-date risk factor assessment improves VA risk stratification.