Does N-Terminal Pro-B-Type Natriuretic Peptide Improve the Risk Stratification of Emergency Department Patients With Syncope?

Ann Intern Med. 2020 May 19;172(10):648-655. doi: 10.7326/M19-3515. Epub 2020 Apr 28.


Background: Studies have reported that natriuretic peptides provide prognostic information for emergency department (ED) syncope.

Objective: To evaluate whether adding N-terminal pro-B-type natriuretic peptide (NT-proBNP) to the Canadian Syncope Risk Score (CSRS) improves prediction of 30-day serious adverse events (SAEs).

Design: Prospective cohort study.

Setting: 6 EDs in 2 Canadian provinces.

Participants: 1452 adult ED patients with syncope.

Intervention: Serum NT-proBNP was measured locally at 1 site and batch processed at a central laboratory from other sites. The concentrations were not available to treating physicians or for adjudication of outcomes.

Measurements: An adjudicated composite outcome of 30-day SAEs, including death and cardiac (arrhythmic and nonarrhythmic) and noncardiac events.

Results: Of 1452 patients enrolled, 152 (10.5% [95% CI, 9.0% to 12.1%]) had 30-day SAEs, 57 (3.9%) of which were identified after the index ED disposition. Serum NT-proBNP concentrations were significantly higher among patients with SAEs than those without them (median, 626.5 ng/L vs. 81 ng/L; P < 0.001). Adding NT-proBNP values to the CSRS did not significantly improve prognostication (c-statistic, 0.89 and 0.90; P = 0.12 for difference), regardless of SAE subgroup or whether the SAE was identified after the index ED visit. The net reclassification index shows that NT-proBNP would have correctly reclassified 3% of patients with SAEs at the expense of incorrectly reclassifying 2% of patients without SAEs.

Limitations: Our study was powered to detect a 3% difference in the area under the curve. The heterogeneity of outcomes and robust baseline discrimination by the CSRS will make improvements challenging.

Conclusion: Although serum NT-proBNP concentrations were generally much higher among ED patients with syncope who had a 30-day SAE, this blood test added little new information to the CSRS. Routine use of NT-proBNP for ED syncope prognostication is not recommended.

Primary funding source: Physicians' Services Incorporated Foundation, Canadian Institutes of Health Research, and The Ottawa Hospital Academic Medical Organization.

Keywords: Arrhythmia; Attention; Cardiovascular therapy; Electrocardiography; Hematologic tests; Hemorrhage; Natriuretic peptide; Research laboratories; Syncope; Troponin.

Publication types

  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers / blood
  • Canada / epidemiology
  • Emergency Service, Hospital*
  • Female
  • Follow-Up Studies
  • Humans
  • Incidence
  • Male
  • Middle Aged
  • Natriuretic Peptide, Brain / blood*
  • Peptide Fragments / blood*
  • Prognosis
  • Prospective Studies
  • Protein Precursors
  • Risk Assessment / methods*
  • Risk Factors
  • Syncope / blood*
  • Syncope / diagnosis
  • Syncope / epidemiology
  • Young Adult


  • Biomarkers
  • Peptide Fragments
  • Protein Precursors
  • pro-brain natriuretic peptide (1-76)
  • Natriuretic Peptide, Brain