Abstract Body (Do not enter title and authors here): Background: Demand ischemia is typically ascribed little importance but likely indicates an elevated cardiovascular risk that is more significant than current convention dictates, despite the absence of plaque rupture.

Hypothesis: Demand ischemia likely predicts worse 3-month cardiovascular outcomes in patients with nonocclusive CAD admitted for nonsevere sepsis.

Methods: We conducted a retrospective cohort study using data from the National Readmissions Database 2017 to 2020 to evaluate whether demand ischemia predicts increased risk of 3-month readmission with adverse cardiovascular outcomes in patients with nonocclusive CAD admitted for nonsevere sepsis. The outcomes of interest were 3-month readmissions with acute heart failure, ventricular tachyarrhythmia, cardiogenic shock, STEMI, acute respiratory failure, AKI and vasopressor use. Multivariate analysis was employed to derive adjusted odds ratios (OR) after accounting for age, Charlson comorbidity index, household income, hospital location and size, hypertension, diabetes mellitus, hyperlipidemia, CHF, atrial fibrillation/flutter, CKD, tobacco use, anemia, malnutrition, obesity, OSA and OHS.

Results: Among patients with nonocclusive CAD admitted for nonsevere sepsis, 717,110 did not have demand ischemia, compared to 25,728 patients who did. In patients with demand ischemia, our results showed significantly increased risk of 3-month readmission with acute heart failure (OR 2.10, P < 0.0005, CI 2.00 – 2.19), ventricular tachyarrhythmia (OR 2.51, P < 0.0500, CI 1.19 – 5.34), cardiogenic shock (OR 1.66, P < 0.0005, CI 1.45 - 1.90), acute respiratory failure (OR 1.97, P < 0.0005, CI 1.89 – 2.05), AKI (OR 1.48, P < 0.0005, CI 1.42 – 1.54) and vasopressor use (OR 1.52, P < 0.0005, CI 1.31 – 1.78) There were no cases of 3-month readmissions with STEMI, possibly due to coding.

Conclusion: Our results indicate that despite being considered a relatively benign diagnosis, demand ischemia is likely actually a marker for meaningfully elevated cardiovascular risk. Further studies will be needed to support this idea and to identify interventions that mitigate the risk.