A systematic review 1 including 20 studies with a total of 9 702 subjects was abstracted in DARE. The studies assessed the diagnostic accuracy of brain natriuretic peptide (BNP), including a comparison with atrial natriuretic peptide (ANP). The included studies used a variety of reference standards which the review categorised into the following groups: left ventricular ejection fraction (LVEF) less than 30%; LVEF less than 40%; LVEF less than 45 to 55%; clinical diagnosis; diastolic failure; systolic or diastolic failure. LVEF less than 40% (8 studies): the pooled diagnostic odds ratio (DOR) was 11.6 (95% CI: 8.4 to 16.1). Pooling only those studies that used a cut-off for BNP of between 14 and 19 pmol/L (5 studies) gave an estimated positive LR of 4.1 (95% CI: 2.6 to 6.6) and a negative LR of 0.35 (95% CI: 0.17 to 0.72). LVEF 45 to 55% (7 studies): the pooled DOR was 5.6 (95% CI: 3.7 to 8.5) but there was statistically significant heterogeneity (P<0.01). Clinical criteria (7 studies): the pooled DOR was 30.9 (95% CI: 27.0 to 35.4). The largest study in this group had a cut-off for BNP of 14.4 pmol/L with a positive LR of 2.6 (95% CI: 2.3 to 2.8) and a negative LR of 0.05 (95% CI: 0.03 to 0.07). Diastolic failure (3 studies): the pooled DOR 28.3 (95% CI: 2.66 to 300.5), but there was significant heterogeneity (P<0.001). Systolic or diastolic failure (2 studies): the pooled DOR was 37.7 (95% CI: 5.9 to 237.2) but there was significant heterogeneity (P=0.02). There was no significant difference between the pooled DORs of studies carried out in general practice or community settings and those performed in hospital. The 3 studies comparing the diagnostic accuracy of BNP with N-terminal ANP found BNP to be marginally more accurate as a diagnostic marker of heart failure (P=0.048). The authors concluded that BNP is an accurate marker of heart failure, and use of a cutoff value of 15 pmol/L achieves high sensitivity, and BNP values below this exclude heart failure in patients in whom disease is suspected.
Another study 2 evaluated the use of age-related decision limits for N-terminal pro-B-type natriuretic peptide (NT-proBNP), for ruling out suspected systolic dysfunction in symptomatic patients in primary care, compared with the present standards. 10 studies (n=5 508) with NT-proBNP analysis and echocardiography were included with median age of 62 years and prevalence of reduced left ventricular systolic function (LVEF ≤ 40%) of 18%. In a receiver operating characteristic curve analysis, overall area under the curve (AUC) was 0.89. AUC was highest (0.95) for <50 years, intermediate (0.90) for 50-75 years, and lowest (0.82) for >75 years. Using optimized decision limits, sensitivity, specificity, and negative predictive values (NPVs) were: <50 years (50 ng/L): 99.2, 57.2, and 99.7%; 50-75 years (75 ng/L): 95.9, 51.0, and 96.8%; and >75 years (250 ng/L): 87.9, 53.7, and 92.4%, respectively. Using only a single decision value (125 ng/L for all ages) gave sensitivities of 89.1, 91.9, and 94.3%; specificities of 84.0, 69.1, and 29.3% and NPVs of 97.7, 97.6, and 93.4%.
Comment: The quality of evidence is downgraded by inconsistency (variability in results across studies and heterogeneity in the reported outcomes).
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