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Background: The epidemiology and outcomes of infective endocarditis (IE) may be changing due to increasing transcatheter valve replacements and intravenous drug use. Our goal was to evaluate the demographics and outcomes of patients with IE using the largest sample of IE patients published to date.Methods: We used the Nationwide Readmissions Database, which compiles all-payer hospital inpatient stays across 22 states - a sample size of 13 to 15 million discharges per year. We identified hospitalization for IE from 2010 to 2015 using International Classification of Diseases (ICD) codes. The primary outcomes of interest were annual IE incidence, and in-hospital death rates, valve replacement, and 30-day readmission rates.Results: We identified 164,542 hospitalized IE cases from 2010 to 2015. Incidence ranged from 6 to 121 cases per 100,000 adults, with incidence increasing with age. Overall, 10.6% (17,420 of 164,542) of patients died during the index hospitalization, with lowest mortality amongst youngest patients, 4.7% (449 of 9,600) in 18-29 age group compared with 10.8% (4,449 of 41,255) amongst patients aged 80 and older. Among index hospitalization survivors, 9.6% (14,165 of 147,122) were re-hospitalized within 30 days. In contrast to mortality, re-hospitalization was 14% (1,285 of 9,151) among 18-29 year olds vs. 6.4% (2,365 of 36,806) in the 80+ age group. Valve replacement occurred during the index hospitalization for 7.9% (12,950 of 164,542) of IE patients. Valve replacement was least common in older age groups; 13.6% (4,881 of 35,678) of those 18-49 years old received valve replacements compared with only 1.3% (524 of 41,255) of patients age 80 and older.Conclusion: Infective endocarditis incidence increases with age, with an incidence more than twenty-fold higher in those age 80 and older compared with 18-29 year olds. Moreover, older age is associated with higher rates of IE-related mortality, but lower rates of surgery and readmission.