Substance Use-Associated Infective Endocarditis Mortality in Young U.S. Adults, 2018 to 2024.

BACKGROUND: Substance use is a major driver of infective endocarditis (IE) in young U.S. adults, but recent national mortality trends remain unclear. OBJECTIVES: The objective of the study was to characterize trends in substance use-associated IE (SU-IE) mortality among U.S. adults aged 25 to 44 years, with expanded and sensitivity analyses. METHODS: We analyzed Centers for Disease Control and Prevention Wide-ranging Online Data for Epidemiologic Research Multiple Cause of Death data from 2018 to 2024. IE-associated deaths were identified using International Classification of Diseases-10th Revision codes I33.0, I33.9, and I38; SU-IE required concurrent F11, F12, F13, F14, F15, or F19 codes. Mortality rates, overlap proportions, subgroup trends, and joinpoint annual percent changes with 95% CIs were assessed. RESULTS: Among 9,745 IE-associated deaths in adults aged 25 to 44 years, 3,756/9,745 (38.5%) had substance-use overlap. Annual SU-IE deaths peaked at 655/1,604 (40.8%) in 2020 and 655/1,643 (39.9%) in 2021, then declined to 338/1,051 (32.2%) in 2024. The age-adjusted rate decreased from 0.75 per 100,000 (95% CI: 0.69-0.80) in 2021 to 0.41 (95% CI: 0.37-0.45) in 2024. Overlap decreased from 604/1,447 (41.7%) in 2018 to 338/1,051 (32.2%) in 2024. Significant post-2021 declines occurred among females (annual percent change, -23.59%), adults aged 25 to 34 years (-31.73%), adults aged 35 to 44 years (-12.55%), and White adults (-23.46%). American Indian or Alaska Native adults had the highest rates, and nonurban counties exceeded large central metropolitan counties. Among adults aged ≥25 years, 5,967/115,096 (5.2%) IE-associated deaths met the SU-IE criteria, including 2,211/5,967 (37.1%) among those aged ≥45 years. CONCLUSIONS: SU-IE mortality in young U.S. adults declined after 2021 but remained marked by demographic and geographic disparities.