Neurofilament Light Chain and Glial Fibrillary Acidic Protein as early prognostic biomarkers after out-of-hospital cardiac arrest

TY - JOUR

T1 - Neurofilament Light Chain and Glial Fibrillary Acidic Protein as early prognostic biomarkers after out-of-hospital cardiac arrest

AU - Klitholm, Maibritt

AU - Jeppesen, Anni Nørgaard

AU - Christensen, Steffen

AU - Parkner, Tina

AU - Tybirk, Lea

AU - Kirkegaard, Hans

AU - Sandfeld-Paulsen, Birgitte

AU - Grejs, Anders Morten

N1 - Publisher Copyright: © 2023 Elsevier B.V.

PY - 2023/12

Y1 - 2023/12

N2 - AIMS: Neurofilament Light Chain (NfL) and Glial Fibrillary Acidic Protein (GFAP) are proteins released into the bloodstream upon hypoxic brain injury. We evaluated the biokinetics and examined the prognostic performance of serum NfL and GFAP in comatose out-of-hospital cardiac arrest (OHCA) patients. Furthermore, we compared the prognostic performance to that of serum Neuron Specific Enolase (NSE).METHODS: This is a sub-study of the "Targeted temperature management for 48 vs 24 hours" (NCT01689077) trial. NfL and GFAP serum values from 82 patients were examined in blood samples collected at 24, 48 and 72 hours (h) after reaching target temperature of 33 ± 1 °C. This temperature was reached within a median of 281-320 minutes after intensive care unit admission. GFAP was analysed at 48 and 72 h. The neuroprognostic performance of NfL and GFAP was evaluated after 6 months follow-up.RESULTS: NfL and GFAP values were significantly higher in patients with a poor outcome (Cerebral Performance Category (CPC) score 3-5) vs. good outcome (CPC 1-2). NfL 24 h: 1371.5 (462.0; 2125.1) vs. 24.8 (14.0; 61.6). GFAP 48 h: 1285.3 (843.9; 2236.7) vs. 361.2 (200.4; 665.6) (both p < 0.001). Both biomarkers were promising markers of poor functional outcome at 24 and 48 h respectively: NfL 24 h: AUROC 0.95 (95% CI: 0.91-1.00). GFAP 48 h: AUROC 0.88 (95% CI: 0.81-0.96). NfL and GFAP both predicted outcome better than NSE at 48 h (both p < 0.01). At 72 h NfL but not GFAP outperformed NSE (p = 0.01).CONCLUSION: Serum NfL and GFAP may be strong biomarkers of poor functional outcome after OHCA from an early timepoint.

AB - AIMS: Neurofilament Light Chain (NfL) and Glial Fibrillary Acidic Protein (GFAP) are proteins released into the bloodstream upon hypoxic brain injury. We evaluated the biokinetics and examined the prognostic performance of serum NfL and GFAP in comatose out-of-hospital cardiac arrest (OHCA) patients. Furthermore, we compared the prognostic performance to that of serum Neuron Specific Enolase (NSE).METHODS: This is a sub-study of the "Targeted temperature management for 48 vs 24 hours" (NCT01689077) trial. NfL and GFAP serum values from 82 patients were examined in blood samples collected at 24, 48 and 72 hours (h) after reaching target temperature of 33 ± 1 °C. This temperature was reached within a median of 281-320 minutes after intensive care unit admission. GFAP was analysed at 48 and 72 h. The neuroprognostic performance of NfL and GFAP was evaluated after 6 months follow-up.RESULTS: NfL and GFAP values were significantly higher in patients with a poor outcome (Cerebral Performance Category (CPC) score 3-5) vs. good outcome (CPC 1-2). NfL 24 h: 1371.5 (462.0; 2125.1) vs. 24.8 (14.0; 61.6). GFAP 48 h: 1285.3 (843.9; 2236.7) vs. 361.2 (200.4; 665.6) (both p < 0.001). Both biomarkers were promising markers of poor functional outcome at 24 and 48 h respectively: NfL 24 h: AUROC 0.95 (95% CI: 0.91-1.00). GFAP 48 h: AUROC 0.88 (95% CI: 0.81-0.96). NfL and GFAP both predicted outcome better than NSE at 48 h (both p < 0.01). At 72 h NfL but not GFAP outperformed NSE (p = 0.01).CONCLUSION: Serum NfL and GFAP may be strong biomarkers of poor functional outcome after OHCA from an early timepoint.

KW - Cardiac arrest

KW - Glial Fibrillary Acidic Protein

KW - Neurofilament Light Chain

KW - Neuroprognostication

KW - Prognosis

KW - Prospective Studies

KW - Intermediate Filaments

KW - Humans

KW - Biomarkers

KW - Neurofilament Proteins

KW - Out-of-Hospital Cardiac Arrest/therapy

UR - https://www.scopus.com/pages/publications/85173700044

U2 - 10.1016/j.resuscitation.2023.109983

DO - 10.1016/j.resuscitation.2023.109983

M3 - Journal article

C2 - 37778613

AN - SCOPUS:85173700044

SN - 0300-9572

VL - 193

JO - Resuscitation

JF - Resuscitation

M1 - 109983

ER -