Diagnostic Accuracy of Natriuretic Peptides for Heart Failure in Patients with Pleural Effusion: A Systematic Review and Updated Meta-Analysis

<div><p>Background</p><p>Previous studies have reported that natriuretic peptides in the blood and pleural fluid (PF) are effective diagnostic markers for heart failure (HF). These natriuretic peptides include N-terminal pro-brain natriuretic peptide (NT-proBNP), brain natriuretic peptide (BNP), and midregion pro-atrial natriuretic peptide (MR-proANP). This systematic review and meta-analysis evaluates the diagnostic accuracy of blood and PF natriuretic peptides for HF in patients with pleural effusion.</p><p>Methods</p><p>PubMed and EMBASE databases were searched to identify articles published in English that investigated the diagnostic accuracy of BNP, NT-proBNP, and MR-proANP for HF. The last search was performed on 9 October 2014. The quality of the eligible studies was assessed using the revised Quality Assessment of Diagnostic Accuracy Studies tool. The diagnostic performance characteristics (sensitivity, specificity, and other measures of accuracy) were pooled and examined using a bivariate model.</p><p>Results</p><p>In total, 14 studies were included in the meta-analysis, including 12 studies reporting the diagnostic accuracy of PF NT-proBNP and 4 studies evaluating blood NT-proBNP. The summary estimates of PF NT-proBNP for HF had a diagnostic sensitivity of 0.94 (95% confidence interval [CI]: 0.90–0.96), specificity of 0.91 (95% CI: 0.86–0.95), positive likelihood ratio of 10.9 (95% CI: 6.4–18.6), negative likelihood ratio of 0.07 (95% CI: 0.04–0.12), and diagnostic odds ratio of 157 (95% CI: 57–430). The overall sensitivity of blood NT-proBNP for diagnosis of HF was 0.92 (95% CI: 0.86–0.95), with a specificity of 0.88 (95% CI: 0.77–0.94), positive likelihood ratio of 7.8 (95% CI: 3.7–16.3), negative likelihood ratio of 0.10 (95% CI: 0.06–0.16), and diagnostic odds ratio of 81 (95% CI: 27–241). The diagnostic accuracy of PF MR-proANP and blood and PF BNP was not analyzed due to the small number of related studies.</p><p>Conclusions</p><p>BNP, NT-proBNP, and MR-proANP, either in blood or PF, are effective tools for diagnosis of HF. Additional studies are needed to rigorously evaluate the diagnostic accuracy of PF and blood MR-proANP and BNP for the diagnosis of HF.</p></div

Summary receiver operating characteristic curves for overall diagnostic accuracy of pleural fluid N-terminal pro-brain natriuretic peptide.

<p>Each study in the meta-analysis is represented by a solid circle.</p

Summary of eligible studies.

<p>M: malignancy, TB: tuberculosis, PP: parapneumonic effusion, PE: pulmonary embolism, LC: liver cirrhosis, HF: heart failure, HH: hepatic hydrothorax, NS: nephrotic syndrome, PCABG: postcoronary artery bypass grafting, PCIS: postcardiac injury syndrome, CD: collagen disease</p><p>Summary of eligible studies.</p

Funnel plot for the assessment of publication bias.

<p>Funnel plot for the assessment of publication bias.</p

Forest plot of the estimates of sensitivity and specificity for pleural fluid N-terminal pro-brain natriuretic peptide in the diagnosis of heart failure.

<p>Forest plot of the estimates of sensitivity and specificity for pleural fluid N-terminal pro-brain natriuretic peptide in the diagnosis of heart failure.</p

Diagnostic characteristics reported by eligible studies.

<p>AUC: area under the receiver operating characteristic curve, TP: true-positive rate, FP: false-positive rate, FN: false-negative rate, TN: true-negative rate, 95%CI: 95% confidence interval, PF: pleural fluid, NR: not reported, NT-proBNP: N-terminal pro-brain natriuretic peptide, BNP: brain natriuretic peptide, MR-proANP: midregion pro-atrial natriuretic peptide</p><p>Diagnostic characteristics reported by eligible studies.</p

Overall diagnostic accuracy of blood and pleural fluid NT-proBNP for heart failure.

<p>NT-proBNP: N-terminal pro-brain natriuretic peptide, AUC: area under the receiver operating characteristic curve, 95%CI: 95% confidence interval, PLR: positive likelihood ratio, NLR: negative likelihood ratio, DOR: diagnostic odds ratio</p><p>Overall diagnostic accuracy of blood and pleural fluid NT-proBNP for heart failure.</p