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

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.