Abstract Body (Do not enter title and authors here): Background:
Infective endocarditis (IE) recurrence is common among patients with substance use disorder (SUD) and is often met with repeated cardiac interventions due to their young age and perceived procedural candidacy. However, the impact of such interventions on survival remains unclear, particularly in high-risk populations.

Methods:
We conducted a retrospective cohort study (2014–2024) using ICD codes at a safety-net community hospital in downtown Minneapolis. We stratified patients with SUD into three groups: no IE (n=31231), single IE episode (n=149), and recurrent IE (≥2 episodes; n=35). We compared all-cause mortality, cause of death, mean age, and procedural rates across groups. SUD was defined as opioid, methamphetamine, or cocaine use disorders (OUD, AmUD, & CoUD). Group comparisons used Fisher’s exact test or Welch’s t-test.

Results:
All-cause mortality increased with IE recurrence: 14% in the “no-IE”, 34% in the “single”, and 57% in the “recurrent” groups (p<0.001). The recurrent IE group had a younger age (36.3 ± 9.6 years) with higher cardiac intervention rates (15% in single vs. 20% in multiple IE; p<0.001). In patients with single IE, 40.9% of deaths were SUD-related and 34.3% were IE-related (Figure). In recurrent IE, IE-related deaths were higher (44.8%), but SUD-related deaths remained substantial (40.3%). Notably, over 40% of deaths in both groups were attributed to SUD rather than IE.

Conclusion:
Among patients with recurrent IE and SUD, cardiac procedural interventions are higher and associated with a higher risk of mortality. Over 40% of deaths in this population are attributed to SUD. These observations emphasize the critical importance of individualized, multidisciplinary, and risk-adapted care strategies to address SUD in the complex trajectory of single and recurrent IE, as well as careful determination of utility of cardiac procedural interventions.