Background Individuals eligible for lung cancer screening with low-dose CT face a higher cardiovascular mortality risk. Purpose To investigate the association between changes in epicardial adipose tissue (EAT) at the 2-year interval and mortality in individuals undergoing serial low-dose CT lung cancer screening. Materials and Methods This secondary analysis of the National Lung Screening Trial obtained EAT volume and density from serial low-dose CT scans using a validated automated deep learning algorithm. EAT volume and density changes over 2 years were categorized into typical (decrease of 7% to increase of 11% and decrease of 3% to increase of 2%, respectively) and atypical (increase or decrease beyond typical) changes, which were associated with all-cause, cardiovascular, and lung cancer mortality. Uni- and multivariable Cox proportional hazard regression models-adjusted for baseline EAT values, age, sex, race, ethnicity, smoking, pack-years, heart disease or myocardial infarction, stroke, hypertension, diabetes, education status, body mass index, and coronary artery calcium-were performed. Results Among 20 661 participants (mean age, 61.4 years ± 5.0 [SD]
12 237 male [59.2%]), 3483 (16.9%) died over a median follow-up of 10.4 years (IQR, 9.9-10.8 years) (cardiovascular related: 816 [23.4%]
lung cancer related: 705 [20.2%]). Mean EAT volume increased (2.5 cm