Cardiac arrest & resuscitation
Blood biomarkers for the prediction of outcome after cardiac arrest: an international prospective observational study within the Targeted Hypothermia versus Normothermia after Out-of-Hospital Cardiac Arrest (TTM2) trial
Authors' conclusion
Neurofilament light is a highly accurate predictor of long-term outcome after cardiac arrest and superior to other relevant biomarkers evaluated in this study.
Study context
- Population
- Adults with OHCA of presumed cardiac or unknown cause, unconscious after arrest; serum sampled at 0, 24, 48 and 72 h after ICU admissionof 932 eligible
- Participants
- 819 adults
- Comparison
- Neurofilament light vs glial fibrillary acidic protein, neuron-specific enolase and S100 for outcome prediction
- Primary endpoint
- Good (modified Rankin Scale 0-3) or poor (modified Rankin Scale 4-6) functional outcome; prognostic accuracy by AUROC
- Follow-up
- 6 months
Methodological detailsinternational, 24 European hospitals, pre-specified Bonferroni correction (p<0.0125)
- International
- 24 European hospitals
- Pre-specified Bonferroni correction (p<0.0125)
Primary result
As reported in the abstract
Prediction of functional outcome (AUROC at 0, 24, 48, 72 h)
| Group | AUROC 0 h | AUROC 24 h | AUROC 48 h | AUROC 72 h |
|---|---|---|---|---|
| Neurofilament light | 0.77 (95% CI 0.73-0.80) | 0.92 (0.90-0.94) | 0.93 (0.91-0.95) | 0.93 (0.91-0.95) |
| Glial fibrillary acidic protein | 0.74 (95% CI 0.70-0.77) | 0.87 (0.84-0.90) | 0.87 (0.84-0.90) | 0.87 (0.84-0.91) |
| Neuron-specific enolase | 0.61 (95% CI 0.56-0.65) | 0.78 (0.75-0.82) | 0.85 (0.81-0.88) | 0.86 (0.82-0.89) |
| S100 | 0.74 (95% CI 0.71-0.78) | 0.84 (0.81-0.87) | 0.79 (0.75-0.82) | 0.78 (0.74-0.82) |
AUROC 0 h
Neurofilament light0.77 (95% CI 0.73-0.80)
Glial fibrillary acidic protein0.74 (95% CI 0.70-0.77)
Neuron-specific enolase0.61 (95% CI 0.56-0.65)
S1000.74 (95% CI 0.71-0.78)
AUROC 24 h
Neurofilament light0.92 (0.90-0.94)
Glial fibrillary acidic protein0.87 (0.84-0.90)
Neuron-specific enolase0.78 (0.75-0.82)
S1000.84 (0.81-0.87)
AUROC 48 h
Neurofilament light0.93 (0.91-0.95)
Glial fibrillary acidic protein0.87 (0.84-0.90)
Neuron-specific enolase0.85 (0.81-0.88)
S1000.79 (0.75-0.82)
AUROC 72 h
Neurofilament light0.93 (0.91-0.95)
Glial fibrillary acidic protein0.87 (0.84-0.91)
Neuron-specific enolase0.86 (0.82-0.89)
S1000.78 (0.74-0.82)
- Neurofilament light vs Glial fibrillary acidic protein: P < 0.0001 — significantly higher at 24, 48 and 72 h
- Neurofilament light vs Glial fibrillary acidic protein: P = 0.27 — not significant at 0 h
Original publication
Blood biomarkers for the prediction of outcome after cardiac arrest: an international prospective observational study within the Targeted Hypothermia versus Normothermia after Out-of-Hospital Cardiac Arrest (TTM2) trial. Lancet Respir Med. Published 11 December 2025. doi:10.
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