Biomarkers of Heart Failure in Pleural Fluid


      The objective of this study was to compare the diagnostic accuracy of pleural fluid brain natriuretic peptide (BNP), N-terminal pro-BNP (NT-pro-BNP) and ST2, which are biomarkers of myocyte stress, for diagnosing pleural effusions due to heart failure (HF). BNP and ST2 have not been previously evaluated in pleural fluid.


      The three biomarkers were measured in the pleural fluid of 90 cardiac effusions and 91 noncardiac effusions by commercially available methodologies. The area under the curve (AUC) quantified the overall diagnostic accuracy of the tests.


      Pleural fluid NT-pro-BNP, BNP, and ST2 demonstrated AUCs of 0.96, 0.90 and 0.59, respectively, for diagnosing effusions due to HF. The cutoff values of 1,300 and 115 pg/mL, respectively, for NT-pro-BNP and BNP had the best discriminating properties. The reference level for BNP was particularly accurate in men > 75 years of age (AUC, 0.98), but age, gender, and serum creatinine level did not influence the NT-pro-BNP levels. Of the 20 patients whose cardiac effusions were misclassified as exudates by the criteria of Light et al, 18 patients (90%) and 14 patients (70%), respectively, would have been correctly categorized by NT-pro-BNP and BNP, whereas only 10 patients (50%) would have been appropriately classified by the serum-pleural protein gradient.


      The pleural fluid NT-pro-BNP level is very useful in establishing the diagnosis of HF-associated effusions, and it confirms this diagnosis better than pleural BNP levels. The measurement of NT-pro-BNP rather than the serum-to-pleural protein gradient is recommended for identifying mislabeled cardiac transudates. The pleural fluid ST2 level is not helpful in diagnosing HF.
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        • Tang WH
        • Francis GS
        • Morrow DA
        • et al.
        National Academy of Clinical Biochemistry Laboratory Medicine practice guidelines: clinical utilization of cardiac biomarker testing in heart failure.
        Clin Biochem. 2008; 41: 210-221
        • Porcel JM
        The use of probrain natriuretic peptide in pleural fluid for the diagnosis of pleural effusions resulting from heart failure.
        Curr Opin Pulm Med. 2005; 11: 329-333
        • Porcel JM
        Establishing a diagnosis of pleural effusion due to heart failure.
        Respirology. 2007; 12: 654-659
        • Braunwald E
        Biomarkers in heart failure.
        N Engl J Med. 2008; 358: 2148-2159
        • Rehman SU
        • Mueller T
        • Januzzi Jr, JL
        Characteristics of the novel interleukin family biomarker ST2 in patients with acute heart failure.
        J Am Coll Cardiol. 2008; 52: 1458-1465
        • Porcel JM
        • Chorda J
        • Cao G
        • et al.
        Comparing serum and pleural fluid pro-brain natriuretic peptide (NT-proBNP) levels with pleural-to-serum albumin gradient for the identification of cardiac effusions misclassified by Light's criteria.
        Respirology. 2007; 12: 654-659
        • Kapoor JR
        • Perazella MA
        Diagnostic and therapeutic approach to acute decompensated heart failure.
        Am J Med. 2007; 120: 121-127
        • Light RW
        Pleural effusion.
        N Engl J Med. 2002; 346: 1971-1977
        • Hanley JA
        • McNeil BJ
        A method of comparing the areas under receiver operating characteristic curves derived from the same cases.
        Radiology. 1983; 148: 839-843
      1. R Development Core Team 2008. R: a language and environment for statistical computing. Available at: Accessed July 18, 2009

        • Romero-Candeira S
        • Hernández L
        • Romero-Brufao S
        • et al.
        Is it meaningful to use biochemical parameters to discriminate between transudative and exudative pleural effusions?.
        Chest. 2002; 122: 1524-1529
        • Porcel JM
        • Vives M
        • Cao G
        • et al.
        Measurement of pro-brain natriuretic peptide in pleural fluid for the diagnosis of pleural effusions due to heart failure.
        Am J Med. 2004; 116: 417-420
        • Tomcsányi J
        • Nagy E
        • Somlói M
        • et al.
        NT-brain natriuretic peptide levels in pleural fluid distinguish between pleural transudates and exudates.
        Eur J Heart Fail. 2004; 6: 753-756
        • Gegenhuber A
        • Mueller T
        • Dieplinger B
        • et al.
        Plasma B-type natriuretic peptide in patients with pleural effusions: preliminary observations.
        Chest. 2005; 128: 1003-1009
        • Kolditz M
        • Halank M
        • Schiemanck CS
        • et al.
        High diagnostic accuracy of NT-proBNP for cardiac origin of pleural effusions.
        Eur Respir J. 2006; 28: 144-150
        • Liao H
        • Na MJ
        • Dikensoy O
        • et al.
        Diagnostic value of pleural fluid N-terminal pro-brain natriuretic peptide levels in patients with cardiovascular diseases.
        Respirology. 2008; 13: 53-57
        • Han CH
        • Choi JE
        • Chung JH
        Clinical utility of pleural fluid NT-pro brain natriuretic peptide (NT-proBNP) in patients with pleural effusions.
        Intern Med. 2008; 47: 1669-1674
        • Seyhan EC
        • Altin S
        • Cetinkaya E
        • et al.
        The importance of pleural fluid and serum NT-proBNP levels in differentiating pleural effusion due to heart failure from other causes of effusion.
        Intern Med. 2009; 48: 287-293
        • Prontera C
        • Zucchelli GC
        • Vittorini S
        • et al.
        Comparison between analytical performances of polyclonal and monoclonal electrochemiluminescence immunoassays for NT-proBNP.
        Clin Chim Acta. 2009; 400: 70-73
        • Rehman SU
        • Januzzi Jr, JL
        Natriuretic peptide testing in clinical medicine.
        Cardiol Rev. 2008; 16: 240-249
        • Ordonez-Llanos J
        • Collinson PO
        • Christenson RH
        Amino-terminal pro-B-type natriuretic peptide: analytic considerations.
        Am J Cardiol. 2008; 101: 9-15

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