Abstract Body (Do not enter title and authors here): Background: Current clinical tools and biomarkers have limited predictive performance for neurological outcomes after cardiac arrest. Novel biomarkers, including kynureninase (KYNU), have the potential to improve neuro-prognostication. Limited data suggest a potential association of KYNU, a key enzyme in tryptophan metabolism, with poor neurological outcome following cardiac arrest.

Methods: Patients admitted to the cardiac intensive care unit (CICU) at Brigham and Women’s Hospital (Boston, MA; 2017-2020) were enrolled in a biorepository with admission blood sampling. In-hospital neurological outcome, including modified Rankin score (mRS), was assessed by structured chart review. KYNU was assayed using the Olink platform (Neurology panel). We performed a case-control study among patients with (n=150) and without (n=81) presenting cardiac arrest and adjusted for age, sex, BMI, eGFR, glial fibrillary acid protein, and the presence of shock. In addition, we evaluated the association between KYNU and poor neurological outcome and mortality among the cohort with cardiac arrest.

Results: Overall, KYNU concentration was significantly associated with cardiogenic shock on admission (p<0.001). KYNU was significantly associated with presenting cardiac arrest with a strong graded relationship across KYNU quartiles in patients with and without shock (Fig 1). Among patients with cardiac arrest, higher presenting KYNU concentration was associated with a pattern of higher risk of poor neurological outcome at discharge (Fig 2). KYNU was also significantly associated with mortality (Q4 vs. Q1: OR 2.89; 95% CI 1.13-7.70; p=0.029).

Conclusions: KYNU concentrations are elevated following cardiac arrest, and higher concentrations are associated with death and have a tendency toward poor neurological outcomes among patients with cardiac arrest. These data highlight the potential for KYNU as a novel biomarker to inform neuro-prognostication following cardiac arrest.