Primary care REFerral for EchocaRdiogram (REFER) in heart failure: a diagnostic accuracy study

Clare J Taylor, Andrea K Roalfe, Rachel Iles, Fd Richard Hobbs, P Barton, J Deeks, D McCahon, M R Cowie, G Sutton, R C Davis, J Mant, T McDonagh, L Tait, REFER investigators

Research output: Contribution to journalArticle (Academic Journal)peer-review

201 Downloads (Pure)


BACKGROUND: Symptoms of breathlessness, fatigue, and ankle swelling are common in general practice but deciding which patients are likely to have heart failure is challenging.

AIM: To evaluate the performance of a clinical decision rule (CDR), with or without N-Terminal pro-B type natriuretic peptide (NT-proBNP) assay, for identifying heart failure.

DESIGN AND SETTING: Prospective, observational, diagnostic validation study of patients aged >55 years, presenting with shortness of breath, lethargy, or ankle oedema, from 28 general practices in England.

METHOD: The outcome was test performance of the CDR and natriuretic peptide test in determining a diagnosis of heart failure. The reference standard was an expert consensus panel of three cardiologists.

RESULTS: Three hundred and four participants were recruited, with 104 (34.2%; 95% confidence interval [CI] = 28.9 to 39.8) having a confirmed diagnosis of heart failure. The CDR+NT-proBNP had a sensitivity of 90.4% (95% CI = 83.0 to 95.3) and specificity 45.5% (95% CI = 38.5 to 52.7). NT-proBNP level alone with a cut-off <400 pg/ml had sensitivity 76.9% (95% CI = 67.6 to 84.6) and specificity 91.5% (95% CI = 86.7 to 95.0). At the lower cut-off of NT-proBNP <125 pg/ml, sensitivity was 94.2% (95% CI = 87.9 to 97.9) and specificity 49.0% (95% CI = 41.9 to 56.1).

CONCLUSION: At the low threshold of NT-proBNP <125 pg/ml, natriuretic peptide testing alone was better than a validated CDR+NT-proBNP in determining which patients presenting with symptoms went on to have a diagnosis of heart failure. The higher NT-proBNP threshold of 400 pg/ml may mean more than one in five patients with heart failure are not appropriately referred. Guideline natriuretic peptide thresholds may need to be revised.

Original languageEnglish
Pages (from-to)e94-e102
JournalBritish Journal of General Practice
Issue number655
Publication statusPublished - 26 Jan 2017


  • Adult
  • Aged
  • Biomarkers
  • Clinical Protocols
  • Dyspnea
  • Electrocardiography
  • England
  • Fatigue
  • Female
  • Heart Failure
  • Humans
  • Male
  • Middle Aged
  • Natriuretic Peptide, Brain
  • Peptide Fragments
  • Primary Health Care
  • Prospective Studies
  • ROC Curve
  • Referral and Consultation
  • Research Design
  • Journal Article
  • Observational Study
  • Validation Studies


Dive into the research topics of 'Primary care REFerral for EchocaRdiogram (REFER) in heart failure: a diagnostic accuracy study'. Together they form a unique fingerprint.

Cite this