Proteomics-based Multimarker Model Improves Neurofilament Light Chain for Predicting Neurological Outcome after Cardiac Arrest

Abstract

Background: Out of hospital cardiac arrest (OHCA) is a life-threatening event. Continuous advances in management increased initial survival, but the rate of favorable neurological outcome remains low. We have previously shown the usefulness of proteomics to identify novel biomarkers to predict this outcome. Neurofilament light chain (NfL), a marker of axonal damage, has since emerged as a promising single marker. The aim of this study was thus to assess the predictive value of NfL and compare it to our established model.Methods: NfL was measured in plasma samples from OHCA drawn at 48 hours after the event using single molecule assays. Neurological function at discharge from ICU was recorded on the cerebral performance category (CPC) scale. Predictive ability was assessed for NfL and compared to an established multimarker model.Results: Seventy patients were included into this analysis, of whom 21 (30%) showed a favorable outcome (CPC 1-2) compared to 49 (70%) with an unfavorable outcome (CPC 3 - 5). NfL increased from CPC 1 to 5 (16.5 pg/ml to 641 pg/ml, p<0.001). NfL alone performed moderately well with an area under the ROC (AUROC) of 79.4%. Prediction was significantly improved by combination of NfL with the established best performing model (F = 6.83, p = 0.01) with an AUROC to 89.7% (p for comparison = 0.017).Conclusion:The combination of NfL with other plasma and clinical markers is superior to that of either model alone and achieves a very good AUROC in this relatively small sample. Trial registration: ClinicalTrials.gov NCT01960699. Registered 08 October 2013.