Abstract
BackgroundA recent study found serum neurofilament light chain (NfL) levels to be strongly associated with poor neurological outcome in patients after cardiac arrest. Our aim was to confirm these findings in an independent validation study and to investigate whether NfL improves the prognostic value of two cardiac arrest-specific risk scores.MethodsThis prospective, single-center study included 164 consecutive adult after out-of-hospital cardiac arrest (OHCA) patients upon intensive care unit admission. We calculated two clinical risk scores (OHCA, CAHP) and measured NfL on admission within the first 24 h using the single molecule array NF-light® assay. The primary endpoint was neurological outcome at hospital discharge assessed with the cerebral performance category (CPC) score.ResultsPoor neurological outcome (CPC > 3) was found in 60% (98/164) of patients, with 55% (91/164) dying within 30 days of hospitalization. Compared to patients with favorable outcome, NfL was 14-times higher in patients with poor neurological outcome (685 ± 1787 vs. 49 ± 111 pg/mL), with an adjusted odds ratio of 3.4 (95% CI 2.1 to 5.6, p < 0.001) and an area under the curve (AUC) of 0.82. Adding NfL to the clinical risk scores significantly improved discrimination of both the OHCA score (from AUC 0.82 to 0.89, p < 0.001) and CAHP score (from AUC 0.89 to 0.92, p < 0.05). Adding NfL to both scores also resulted in significant improvement in reclassification statistics with a Net Reclassification Index (NRI) of 0.58 (p < 0.001) for OHCA and 0.83 (p < 0.001) for CAHP.ConclusionsAdmission NfL was a strong outcome predictor and significantly improved two clinical risk scores regarding prognostication of neurological outcome in patients after cardiac arrest. When confirmed in future outcome studies, admission NfL should be considered as a standard laboratory measures in the evaluation of OHCA patients.
Highlights
Despite the increased survival rates thanks to medical treatments, the mortality and risk for neurological deficits remains high for cardiac arrest patients [1,2,3]
We investigated the prognostic performance of neurofilament light chain (NfL) regarding sensitivity, specificity, positive and negative predictive values and likelihood ratios at three cutoffs (25, 50, 75 pg/ml), which were close to the median NfL as well as the lower and upper interquartile range
Data presented as mean (SD) and median (Inter Quartile Range, IQR).; NfL = Neurofilament Light Chain; AUC = area under the curve; Cardiac Arrest Hospital Prognosis score (CAHP) = Cardiac Arrest Hospital prognosis (-score); CPC = cerebral performance category; of-hospital cardiac arrest (OHCA) = Out-of-Hospital Cardiac Arrest (-score); Odds ratios (OR) = odds ratio; ROC = receiver operating characteristics curve a Adjusted for age, gender, comorbidities p < 0.001) and a multivariate OR of 3.4 after adjusting for age, gender and comorbidities (Table 2)
Summary
Despite the increased survival rates thanks to medical treatments, the mortality and risk for neurological deficits remains high for cardiac arrest patients [1,2,3]. Two scores were developed for cardiac arrest patients including the Out-of-Hospital Cardiac Arrest score (OHCA) and the Cardiac Arrest Hospital Prognosis score (CAHP) [5,6,7]. These scores, still have limited accuracy and, bear the risk of misclassifying patients. The improvement of these clinical scores by the addition of biomarkers reflecting pathophysiologic mechanisms of neural damage is an unmet medical need. A recent study found serum neurofilament light chain (NfL) levels to be strongly associated with poor neurological outcome in patients after cardiac arrest. Our aim was to confirm these findings in an independent valida‐ tion study and to investigate whether NfL improves the prognostic value of two cardiac arrest-specific risk scores
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