title: Multiple biomarker strategy for improved diagnosis of acute heart failure in older patients presenting to the emergency department.
abstract: OBJECTIVE
  Biomarkers can help to identity acute heart failure (AHF) as the cause of symptoms in patients presenting to the emergency department (ED). Older patients may prove a diagnostic challenge due to co-morbidities. Therefore we prospectively investigated the diagnostic performance of N-terminal pro-B-type natriuretic peptide (NT-proBNP) alone or in combination with other biomarkers for AHF upon admission at the ED.
  
  
  METHODS
  302 non-surgical patients aged ≥ 70 years were consecutively enrolled upon admission to the ED. In addition to NT-proBNP, mid-regional pro-adrenomedullin (MR-proADM), mid-regional pro-atrial natriuretic peptide (MR-proANP), C-terminal pro-endothelin-1 (CT-proET-1) and ultra-sensitive C-terminal pro-vasopressin (Copeptin-us) were measured at admission. Two cardiologists independently adjudicated the final diagnosis of AHF after reviewing all available baseline data excluding the biomarkers. We assessed changes in C-index, integrated discrimination improvement (IDI), and net reclassification improvement (NRI) for the multimarker approach.
  
  
  RESULTS
  AHF was diagnosed in 120 (40%) patients (age 81±6 years, 64 men, 56 women). Adding MR-ADM to NT-proBNP levels improved C-index (0.84 versus 0.81; p=0.045), and yielded IDI (3.3%; p=0.002), NRI (17%, p<0.001) and continuous NRI (33.3%; p=0.002). Adding CT-proET-1 to NT-proBNP levels improved C index (0.86 versus 0.81, p=0.031), and yielded robust IDI (12.4%; p<0.001), NRI (31.3%, p<0.001) and continuous NRI (69.9%; p<0.001). No other dual or triple biomarker combination showed a significant improvement of both C-index and IDI.
  
  
  CONCLUSIONS
  In older patients presenting to the ED, the addition of CT-proET-1 or MR-proADM to NT-proBNP improves diagnostic accuracy of AHF. Both dual biomarker approaches offer significant risk reclassification improvement over NT-proBNP.
authors.affiliation: Institute for Biomedicine of Aging, Friedrich-Alexander-University, Nuremberg, Germany philipp.bahrmann@gmail.com.
authors.forename: Philipp
authors.initials: P
authors.lastname: Bahrmann
authors.affiliation: Department of Cardiology, Friedrich-Alexander-University, Erlangen, Germany.
authors.forename: Anke
authors.initials: A
authors.lastname: Bahrmann
authors.affiliation: Department of Medical Informatics, Biometry and Epidemiology, Friedrich-Alexander-University, Erlangen, Germany.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Hofner
authors.affiliation: Department of Emergency and Critical Care Medicine, Paracelsus Medical University, Nuremberg, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Christ
authors.affiliation: Department of Cardiology, Friedrich-Alexander-University, Erlangen, Germany.
authors.forename: Stephan
authors.initials: S
authors.lastname: Achenbach
authors.affiliation: Institute for Biomedicine of Aging, Friedrich-Alexander-University, Nuremberg, Germany.
authors.forename: Cornel Christian
authors.initials: CC
authors.lastname: Sieber
authors.affiliation: Institute for Clinical Chemistry, Laboratory Medicine and Transfusion Medicine, Paracelsus Medical University, Nuremberg, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Bertsch
mesh_terms: D000046:Academic Medical Centers; D000208:Acute Disease; D053607:Adrenomedullin / Q000097:blood*; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging; D009320:Atrial Natriuretic Factor / Q000097:blood*; D015415:Biomarkers / Q000097:blood; D004636:Emergency Service, Hospital; D019332:Endothelin-1 / Q000097:blood*; D005260:Female; D006020:Glycopeptides / Q000097:blood*; D006333:Heart Failure / Q000097:blood / Q000175:diagnosis*; D006801:Humans; D008297:Male; D020097:Natriuretic Peptide, Brain / Q000097:blood*; D010446:Peptide Fragments / Q000097:blood*; D011237:Predictive Value of Tests; D011379:Prognosis; D011446:Prospective Studies; D011498:Protein Precursors / Q000097:blood*; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D012720:Severity of Illness Index
chemical_list: D015415:Biomarkers; C557077:C-terminal proendothelin-1; D019332:Endothelin-1; D006020:Glycopeptides; D010446:Peptide Fragments; D011498:Protein Precursors; C048197:copeptins; C574167:mid-regional pro-adrenomedullin, human; C552580:midregional pro-atrial natriuretic peptide, human; C109794:pro-brain natriuretic peptide (1-76); D020097:Natriuretic Peptide, Brain; D053607:Adrenomedullin; D009320:Atrial Natriuretic Factor
keywords: adrenomedullin; aged; diagnosis; endothelin; heart failure; natriuretic peptides