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

Research output: Contribution to journalArticlepeer-review


  • CJ Taylor
  • F D Richard Hobbs
  • Martin R Cowie
  • Russell C. Davis
  • Theresa McDonagh
  • Jonathan Mant
  • L Tait

Colleges, School and Institutes

External organisations

  • University of Oxford
  • Sandwell and West Birmingham Hospitals NHS Trust


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 over 55 years, presenting with shortness of breath, lethargy or ankle oedema from 28 general practices in England. Method: 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: 304 participants were recruited. 104 (34.2% (95% CI 28.9 to 39.8)) had 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% (38.5% to 52.7%). NT-proBNP level alone with a cut-off less than 400pg/ml, had sensitivity 76.9% (67.6% to 84.6%) and specificity 91.5% (86.7% to 95.0%). At the lower cut-off of NT-proBNP <125pg/ml, sensitivity was 94.2% (95% CI 87.9% to 97.9%) and specificity 49.0% (41.9% to 56.1%). Conclusions: At the low threshold of NT-proBNP<125pg/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 400pg/ml may mean more than one in five patients with heart failure is not appropriately referred. Guideline natriuretic peptide thresholds may need to be revised.


Original languageEnglish
JournalBritish Journal of General Practice
Publication statusAccepted/In press - 21 Sep 2016