AbstractIntroductionCardiac Implantable Electronic Devices (CIEDs) are widely used for the management of advanced heart failure and ventricular arrhythmias. CIED‐Infection (CIED‐I) has very high mortality, especially in the subsets of patients with limited health‐care access and delayed presentation. The purpose of this study is to identify the risk‐predictors mortality in subjects with CIED‐I.MethodsWe performed a retrospective cohort study of a regional database in patients presenting with CIED infections to tertiary care medical centers across Western New York, USA from 2012 to 2020. The clinical outcomes included recurrent device infection (any admission for CIED‐I after the first hospitalization for device infection), septic complications (pulmonary embolism, respiratory failure, septic shock, decompensated HF, acute kidney injury) and mortality outcomes (death during hospitalization, within 30 days from CIED‐I, and within 1 year from CIED‐I). We studied associations between categorical variables and hard outcomes using χ² tests and used one‐way analysis of variance to measure between‐groups differences.ResultsWe identified 296 patients with CIED‐I, among which 218 (74%) were male, 237 (80%) were white and the mean age at the time of infection was 69.2 ± 13.7 years. One‐third of the patients were referred from the regional facilities. Staphylococcus aureus was responsible for most infections, followed by Enterococcus fecalis. On multivariate analysis, the covariates associated with significantly increased mortality risk included referral from regional facility (OR: 2.0;1.0–4.0), hypertension (Odds ratio, OR: 3.2;1.3–8.8), right ventricular dysfunction (OR: 2.6;1.2–5.1), end‐stage renal disease (OR: 2.6;1.1–6.2), immunosuppression (OR: 11.4;2.5–53.3), and septic shock as a complication of CIED‐I (OR: 3.9;1.3–10.8).ConclusionHypertension, right ventricular dysfunction, immunosuppression, and end‐stage renal disease are associated with higher mortality after CIED‐I. Disproportionately higher mortality was also noted in subjects referred from the regional facilities. This underscores the importance of early clinical risk‐assessment, and the need for a robust referral infrastructure to improve patient outcomes.