Trends in Infective Endocarditis Mortality in the United States: 1999 to 2020: A Cause for Alarm

Background: Data on national trends in mortality due to infective endocarditis (IE) in the United States are limited.Methods and Results: Utilizing the multiple causes of death data from the Centers for Disease Control and Prevention's Wide-Ranging Online Data for Epidemiologic Research database from 1999 to 2020, IE and substance use were identified using the International Classification of Diseases, Tenth Revision, Clinical Modification codes. Between 1999 and 2020, the IE-related age-adjusted mortality rates declined. IE-related crude mortality accelerated significantly in the age groups 25-34 years (average annual percentage change, 5.4 [95% CI, 3.1-7.7]; P<0.001) and 35-44 years (average annual percentage change, 2.3 [95% CI, 1.3-3.3]; P<0.001), but remained stagnant in those aged 45-54 years (average annual percentage change, 0.5 [95% CI, -1.9 to 3]; P=0.684), and showed a significant decline in those aged >= 55 years. A concomitant substance use disorder as multiple causes of death in those with IE increased drastically in the 25-44 years age group (P<0.001). The states of Kentucky, Tennessee, and West Virginia showed an acceleration in age-adjusted mortality rates in contrast to other states, where there was predominantly a decline or static trend for IE.Conclusions: Age-adjusted mortality rates due to IE in the overall population have declined. The marked acceleration in mortality in the 25- to 44-year age group is a cause for alarm. Regional differences with acceleration in IE mortality rates were noted in Kentucky, Tennessee, and West Virginia. We speculate that this acceleration was likely due mainly to the opioid crisis that has engulfed several states and involved principally younger adults.