title: Quantifying the added value of BNP in suspected heart failure in general practice: an individual patient data meta-analysis.
abstract: BACKGROUND
  Diagnosing early stages of heart failure with mild symptoms is difficult. B-type natriuretic peptide (BNP) has promising biochemical test characteristics, but its diagnostic yield on top of readily available diagnostic knowledge has not been sufficiently quantified in early stages of heart failure.
  
  
  OBJECTIVE
  To quantify the added diagnostic value of BNP for the diagnosis of heart failure in a population relevant to GPs and validate the findings in an independent primary care patient population.
  
  
  METHODS
  Individual patient data meta-analysis followed by external validation. The additional diagnostic yield of BNP above standard clinical information was compared with ECG and chest x-ray results.
  
  
  METHODS
  Derivation was performed on two existing datasets from Hillingdon (n=127) and Rotterdam (n=149) while the UK Natriuretic Peptide Study (n=306) served as validation dataset. Included were patients with suspected heart failure referred to a rapid-access diagnostic outpatient clinic. Case definition was according to the ESC guideline. Logistic regression was used to assess discrimination (with the c-statistic) and calibration.
  
  
  RESULTS
  Of the 276 patients in the derivation set, 30.8% had heart failure. The clinical model (encompassing age, gender, known coronary artery disease, diabetes, orthopnoea, elevated jugular venous pressure, crackles, pitting oedema and S3 gallop) had a c-statistic of 0.79. Adding, respectively, chest x-ray results, ECG results or BNP to the clinical model increased the c-statistic to 0.84, 0.85 and 0.92. Neither ECG nor chest x-ray added significantly to the 'clinical plus BNP' model. All models had adequate calibration. The 'clinical plus BNP' diagnostic model performed well in an independent cohort with comparable inclusion criteria (c-statistic=0.91 and adequate calibration). Using separate cut-off values for 'ruling in' (typically implying referral for echocardiography) and for 'ruling out' heart failure--creating a grey zone--resulted in insufficient proportions of patients with a correct diagnosis.
  
  
  CONCLUSIONS
  BNP has considerable diagnostic value in addition to signs and symptoms in patients suspected of heart failure in primary care. However, using BNP alone with the currently recommended cut-off levels is not sufficient to make a reliable diagnosis of heart failure.
authors.affiliation: Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, GA, Utrecht, The Netherlands. hans.kelder@gmail.com
authors.forename: Johannes C
authors.initials: JC
authors.lastname: Kelder
authors.forename: Martin R
authors.initials: MR
authors.lastname: Cowie
authors.forename: Theresa A
authors.initials: TA
authors.lastname: McDonagh
authors.forename: Suzanna M C
authors.initials: SM
authors.lastname: Hardman
authors.forename: Diederick E
authors.initials: DE
authors.lastname: Grobbee
authors.forename: Bernard
authors.initials: B
authors.lastname: Cost
authors.forename: Arno W
authors.initials: AW
authors.lastname: Hoes
mesh_terms: D000368:Aged; D015415:Biomarkers / Q000097:blood; D004562:Electrocardiography; D005194:Family Practice; D005260:Female; D006333:Heart Failure / Q000175:diagnosis*; D006801:Humans; D008297:Male; D020097:Natriuretic Peptide, Brain / Q000097:blood*; D019095:Point-of-Care Systems; D012680:Sensitivity and Specificity
chemical_list: D015415:Biomarkers; D020097:Natriuretic Peptide, Brain