title: No Added Value of Novel Biomarkers in the Diagnostic Assessment of Patients Suspected of Acute Coronary Syndrome.
abstract: BACKGROUND
  Despite the availability of high-sensitive troponin (hs-cTnT), there is still room for improvement in the diagnostic assessment of patients suspected of acute coronary syndrome (ACS). Apart from serial biomarker testing, which is time-consuming, novel biomarkers like copeptin have been proposed to expedite the early diagnosis of suspected ACS in addition to hs-cTnT. We determined whether placenta derived growth factor (PlGF), soluble Fms-like tyrosine kinase 1 (sFlt-1), myoglobin, N-terminal prohormone B-type Natriuretic Peptide (NT-proBNP), growth-differentiation factor 15 (GDF-15) and copeptin improved early assessment of chest pain patients.
  
  
  METHODS
  This prospective, single centre diagnostic FAME-ER study included patients presenting to the ED with symptoms suggestive of ACS. Blood was collected to measure biomarkers, notably, hs-cTnT was retrospectively assessed. Added value of markers was judged by increase in AUC using multivariable logistic regression.
  
  
  RESULTS
  Of 453 patients enrolled, 149 (33%) received a final diagnosis of ACS. Hs-cTnT had the highest diagnostic value in both univariable and multivariable analysis. PPVs of the biomarkers ranged from 23.5% (PlGF) to 77.9% (hs-cTnT), NPVs from 67.0% (PlGF) to 86.4% (hs-cTnT). Only myoglobin yielded diagnostic value in addition to clinical symptoms and electrocardiography (ECG) (AUC of clinical model 0.80) with AUC of 0.84 (p<0.001). However, addition of hs-cTnT was superior (AUC 0.89, p<0.001). Addition of the biomarkers to our clinical model and hs-cTnT did not or only marginally (GDF-15) improved diagnostic performance.
  
  
  CONCLUSIONS
  When assessing patients suspected of ACS, only myoglobin had added diagnostic value beyond clinical symptoms and ECG. However, when combined with hs-cTnT, it yields no additional diagnostic value. PlGF, sFlt-1, NT-proBNP, GDF-15 and copeptin had no added value to the clinical model or hs-cTnT.
authors.affiliation: Julius Center for Health Sciences and Primary Care, University Medical Center, Universiteitsweg 100, 3584 CG, Utrecht, the Netherlands.
authors.forename: Judith M
authors.initials: JM
authors.lastname: Poldervaart
authors.affiliation: Faculty of Medicine, Utrecht University, Universiteitsweg 98, 3584 CG, Utrecht, the Netherlands.
authors.forename: Emma
authors.initials: E
authors.lastname: Röttger
authors.affiliation: Department of Cardiology, Isala Clinics, Dokter van Heesweg 2, 8025 AB, Zwolle, the Netherlands; Department of Cardiology, Meander Medical Center, Maatweg 3, 3813 TZ, Amersfoort, the Netherlands.
authors.forename: Marieke S
authors.initials: MS
authors.lastname: Dekker
authors.affiliation: Julius Center for Health Sciences and Primary Care, University Medical Center, Universiteitsweg 100, 3584 CG, Utrecht, the Netherlands.
authors.forename: Nicolaas P A
authors.initials: NP
authors.lastname: Zuithoff
authors.affiliation: Department of Cardiology, Meander Medical Center, Maatweg 3, 3813 TZ, Amersfoort, the Netherlands.
authors.forename: Peter W H M
authors.initials: PW
authors.lastname: Verheggen
authors.affiliation: Department of Cardiology, Meander Medical Center, Maatweg 3, 3813 TZ, Amersfoort, the Netherlands.
authors.forename: Evelyn A
authors.initials: EA
authors.lastname: de Vrey
authors.affiliation: Department of Cardiology, Meander Medical Center, Maatweg 3, 3813 TZ, Amersfoort, the Netherlands.
authors.forename: Thierry X
authors.initials: TX
authors.lastname: Wildbergh
authors.affiliation: Department of Cardiology, Isala Clinics, Dokter van Heesweg 2, 8025 AB, Zwolle, the Netherlands.
authors.forename: Arnoud W J
authors.initials: AW
authors.lastname: van 't Hof
authors.affiliation: Department of Cardiology, Meander Medical Center, Maatweg 3, 3813 TZ, Amersfoort, the Netherlands.
authors.forename: Arend
authors.initials: A
authors.lastname: Mosterd
authors.affiliation: Julius Center for Health Sciences and Primary Care, University Medical Center, Universiteitsweg 100, 3584 CG, Utrecht, the Netherlands.
authors.forename: Arno W
authors.initials: AW
authors.lastname: Hoes
mesh_terms: D054058:Acute Coronary Syndrome / Q000097:blood / Q000175:diagnosis*; D000368:Aged; D019540:Area Under Curve; D015415:Biomarkers / Q000097:blood*; D004562:Electrocardiography; D005260:Female; D006020:Glycopeptides / Q000097:blood; D055436:Growth Differentiation Factor 15 / Q000097:blood; D006801:Humans; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D020097:Natriuretic Peptide, Brain / Q000097:blood; D016017:Odds Ratio; D010446:Peptide Fragments / Q000097:blood; D000072483:Placenta Growth Factor; D011257:Pregnancy Proteins / Q000097:blood; D011446:Prospective Studies; D012372:ROC Curve; D012680:Sensitivity and Specificity; D020107:Troponin T / Q000097:blood; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000097:blood
chemical_list: D015415:Biomarkers; C526140:GDF15 protein, human; D006020:Glycopeptides; D055436:Growth Differentiation Factor 15; C000608036:PGF protein, human; D010446:Peptide Fragments; D011257:Pregnancy Proteins; D020107:Troponin T; C048197:copeptins; C109794:pro-brain natriuretic peptide (1-76); D020097:Natriuretic Peptide, Brain; D000072483:Placenta Growth Factor; C501162:FLT1 protein, human; D040281:Vascular Endothelial Growth Factor Receptor-1