THE DIAGNOSTIC VALUE OF BNP AND LIGHT S CRITERIA ON HEART FAILURE IN PATIENTS WITH BILATERAL PLEURAL EFFUSION

Size: px

Start display at page:

Download "THE DIAGNOSTIC VALUE OF BNP AND LIGHT S CRITERIA ON HEART FAILURE IN PATIENTS WITH BILATERAL PLEURAL EFFUSION"

Geraldine Baker
6 years ago
Views:

1 Acta Medica Mediterranea, 2016, 32: 1779 THE DIAGNOSTIC VALUE OF BNP AND LIGHT S CRITERIA ON HEART FAILURE IN PATIENTS WITH BILATERAL PLEURAL EFFUSION BING LIU *,**, XUN DING ***, JIONG YANG *,** * Department of Respiratory Medicine, Zhongnan Hospital of Wuhan University, Wuhan, Hubei, , China - ** The Second Clinical Medicine College of Wuhan University, Wuhan, Hubei, , China - *** Department of Radiology, Zhongnan Hospital of Wuhan University, Wuhan, Hubei, , China ABSTRACT Introduction: Heart failure (HF) is one of the major condition able to determine bilateral pleural effusion. The diagnostic value of combined use of Brain natriuretic peptide (BNP) and Light s criteria in the diagnosis of HF is unclear. Materials and methods: 109 patients with both heart failure and bilateral pleural were included in this study. Serum BNP, pleural effusion character were analyzed. The diagnostic sensitivity and specificity of BNP and Light s criteria in the diagnosis of HF were analyzed. Results: 109 patients were included. Serum BNP and percentage of Light s negative patients are higher in patients with HF than those without. When combining BNP positive with Light s criteria together, the diagnostic sensitivity increased to 86.8%. BNP negative together with Light s positive had a good exclusive diagnostic value. The cutoff value of BNP was proved to be pg/ml the diagnosis of HF for patients with bilateral pleural effusion. Conclusion: Combined use of BNP and Light s criteria could increase the diagnostic sensitivity in patients with bilateral pleural effusion and could help recognize those without HF. For patients with bilateral pleural effusion, serum BNP test should be the initial test to recognize and differentially diagnose HF. Keywords: BNP, Light s Criteria, heart failure, bilateral pleural effusion. DOI: / _2016_6_163 Received May 30, 2016; Accepted September 02, 2016 Introduction Heart failure (HF) is a major public health issue and a fatal clinical syndrome, affecting over 23 million people worldwide and the number is still rising (1). Bilateral pleural effusion secondary to HF should be given enough attention, as it will cause very bad prognosis if the patients don t get proper treatment timely. Brain natriuretic peptide (BNP) is a useful marker in the diagnosis of HF (2, 3). BNP has been found to increase in patients with various heart diseases (4). Generally, a cutoff value >400pg/ml is considered as a diagnosis of HF, and a cutoff value <100pg/ml is thought to exclude HF. The serum BNP between 100pg/ml and 400pg/ml is considered as the gray area which needs to be determined together with other diagnostic tests (5, 6). Unfortunately, the BNP level alone could not diagnosis or exclude HF definitely because there are many other factors that could affect its serum concentration, such as age, sex, weight, and renal function (7). Light s criteria are widely used to distinguish exudative pleural effusions from transudative ones (8). The sensitivity and specificity of Light s criteria for the diagnosis of exudates are 98% and 83% individually (9). When classified by Light s criteria, the pleural fluid secondary to HF should be Light s negative, while there are considerable exceptions,

2 1780 Bing Liu, Xun Ding et Al especially for those with a chronic HF and/or administration of diuretic drugs (10). To give the bilateral pleural effusion patients a definite diagnosis whether they have HF or not is difficult sometimes. As both BNP and Light s criteria could help in the diagnosis of HF, we try to investigate the usefulness of their combination on the diagnosis of HF presented by bilateral pleural effusion. Material and methods Patients This study was conducted at Zhongnan Hospital of Wuhan University. All patients were adult (>18 years old) and were admitted to hospital from June 2012 to September The diagnosis of bilateral pleural effusion was confirmed by computed tomography(ct) scan and ultrasound. All patients went through at least one thoracentesis. The pleural effusion tests included cytology, lactic acid dehydrogenase (LDH), adenosine deaminase (ADA), protein, and tumor marker. Serum BNP, total protein, albumin, and LDH were tested as well. All the 109 participants were enrolled only once. Patients with severe renal dysfunction were excluded. This study was approved by the institutional review board (IRB) of Zhongnan Hospital of Wuhan University. Diagnostic criteria of HF The diagnostic criteria of HF were based on the Framingham criteria(11)together with ACCF/AHA Guidelines for the Diagnosis and Management of Heart Failure in Adults (6). Generally, the diagnosis of HF required the simultaneous presence of at least 2 major criteria or 1 major criterion in conjunction with 2 minor criteria according to the Framingham criteria. Meanwhile, the participants underwent chest X-ray and electrocardiogram. Then if the treatment toward HF was effective, the diagnosis of HF could be formed. Light s Criteria and serum BNP The patient would be considered as Light s positive if the pleural effusion met any of the following three standards: 1, The ratio of pleural fluid protein to serum protein is greater than 0.5; 2, The ratio of pleural fluid LDH and serum LDH is greater than 0.6; 3, Pleural fluid LDH is greater than two thirds of the normal upper limit for serum LDH. The patients were classified into BNP positive (BNP>400pg/ml), BNP negative (BNP<100pg/ml) and BNP gray (BNP pg/ml) (12). Statistical analyses Continuous data (age, serum BNP) were presented as mean±sd and differences between groups were performed with student s t test. Non-continuous data were presented as percentage and the differences between groups were performed with X2 text. To assess the diagnostic value of plasma BNP and Light s criteria for the prediction of HF, the diagnostic sensitivity and specificity were calculated. To determine the diagnostic value of BNP, receiver operating characteristic (ROC) curves were constructed and the area under the curve (AUC) was calculated for both measures. Statistical analyses were performed using Statistical Package for the social Sciences (SPSS) 17.0 software (SPSS Statistics for Windows, Version Chicago: SPSS Inc.). The 95% CI and cutoff value of BNP were calculated. All probabilities were two tailed and P values <0.05 were regarded as significant. Results This study enrolled 109 bilateral pleural effusion patients, 68 of whom were diagnosed as HF. There were no age and gender differences between both groups (Table 1). Heart failure non heart failure P value number Age(years old) 74.07± ±12.72 >0.05 Gender(M/F) 45/23 25/16 >0.05 BNP(pg/ml) ± ±63.58 <0.001 Percentage of Light s negative 75.40% 41.55% <0.01 Table 1: General information for patients with bilateral pleural effusion. M: male; F: female Serum BNP level was obviously higher in the HF group than the non-hf group. The percentage of Light s negative patients in HF group was also higher than the non-hf group (Table 1). BNP positive alone had great diagnostic specificity but lower sensitivity in the diagnosis of HF for patients with bilateral pleural effusion. Light s negative alone had relatively low diagnostic sensitivity and specificity.

3 The diagnostic value of BNP and Light s criteria on heart failure in patients with bilateral pleural effusion 1781 When combining BNP positive with Light s criteria together, the diagnostic sensitivity increased dramatically (Table 2). Group Sensitivity Specificity BNP positive 52.90% 100% Light s negative 76.50% 58.50% BNP positive or Light s negative Table 2: Diagnostic sensitivity and specificity of BNP and Light s criteria in all patients. BNP: brain natriuretic peptide BNP negative and Light s positive had a good exclusive diagnostic specificity for patients with bilateral effusion (Table 3). BNP negative and Light s positive 86.80% 75.60% Sensitivity Specificity 70.40% 100% Table 3: Exclusive diagnostic value of BNP and Light s criteria. BNP: brain natriuretic peptide group AUC SE P value Lower limit 95% CI Upper limit When performing ROC analysis, the cutoff value of serum BNP was pg/ml (Table 4 and figure 1A). Cut off value (pg/ml) All patients < Patients in gray area < Table 4: AUC, 95% CI and cut off value of BNP in gray area. AUC: area under the curve; SE: standard error ; CI: confidence interval. Figure 1: ROC curves of serum BNP. (A) ROC curve of serum BNP in all patients; (B) ROC curve of serum BNP in patients whose serum BNP levels were in gray area. ROC: receiver operating characteristic; BNP: brain natriuretic peptide For patients whose serum BNP levels were in the gray area, the diagnostic sensitivity and specificity of Light s negative were 71.4% and 40% respectively. Serum BNP was higher in the HF patients than those without HF (231.2±84.9 vs 160±48.2, P<0.01), and ROC analysis showed that the cutoff value of BNP should be 186.9pg/mL for patients with bilateral effusion in BNP gray area (Table 4, figure 1B). Discussion Bilateral pleural effusion is an important clinical condition with HF as the most frequent contributor (13). It is critical to determine whether the origin of bilateral effusion is HF. The diagnosis of HF should be based on clinical findings together with laboratory test, but it is often difficult to establish with certainty (14). BNP test is largely used in the diagnosis of HF. BNP is synthesized by the ventricles and highly elevated during HF, which correlates well with the HF severity (14). It can also be utilized as an important prognostic indicator in patients with HF (15). Plasma BNP concentrations of patients with pleural effusions of unknown origin may aid in the diagnosis of chronic heart failure (CHF) as the underlying cause (16). A Meta analysis showed that BNP guided therapy could reduce all-cause mortality in patients with CHF (17, 18). An observational study showed that the AUC was for plasma BNP in distinguishing between patients with pleural effusions caused by HF and patients with pleural effusions attributable to other causes (3). This is consistent with our result. Plasma BNP level may be a feasible method as CT scan in the assessment of acute cardiogenic pulmonary edema (19). Light s criteria, which was first described by Light et al, has been proved to have a great value on differentiation transudation from exudation (8, 20). The pleural effusion caused by HF should be transudation. But about 25% of the cases might be misclassified into exudation (21), especially in those with pleural effusions for a long time and the use of diuretics (12, 22). Even though serum-ascites albumin gradient (SAAG) could help differentiate transudation from exudations (23), there are still some drawbacks. In a study about the diagnostic value of serum BNP on HF in the setting of ascites, the authors found that serum BNP was superior to SAAG

4 1782 Bing Liu, Xun Ding et Al and/or total protein concentration in discriminating HF related ascites from other causes (24). Because NT-pro-BNP is more dependent on age, sex, and renal dysfunction (25) and because it is a more expensive test than BNP, so many hospitals test BNP rather than NT-proBNP. In this study, we classified the patients as BNP positive whose serum BNP is higher than 400 pg/ml and BNP negative whose serum BNP is lower than 100pg/ml. We found that all BNP positive patients have HF. And HF could be excluded in all BNP negative patients. We also found that only BNP and only Light s criteria have low diagnostic sensitivity, and combination use of BNP and Light s criteria could increase the diagnostic sensitivity from 52.9% to 86.8 %. For patients whose serum BNP is between 100 pg/ml and 400 pg/ml, Light s criteria could help recognize patients with HF. The origin of bilateral pleural effusion varies based on the character of the pleural effusion. The most common origins for transudation are HF, hypoalbuminemia, liver and renal insufficiency, and cirrhosis, while the most common causes for exudation are pneumonia, lung cancer or other cancers, tuberculosis and lymphoma. Not all the patients need thoracentesis in the first step. We suggested that for the patients with bilateral pleural effusion, especially for those suspected as HF, serum BNP should be measured first (Figure 2). Figure 2:Diagnosis procedure of heart failure for patients with bilateral pleural effusion. Once bilateral pleural effusion happens, determine serum BNP first, then classify the patients into 3 groups. If serum BNP>400pg/ml, HF can be diagnosed. If serum BNP<400pg/ml, perform thoracentesis, and for patients whose serum BNP<100pg/ml and Light positive, heart failure could be excluded. For other patients, Light positive ones should consider pneumonia, cancer, tuberculosis (TB), and rhumatoid arthritis (RA), while Light negative ones should consider hypoalbuminemia, liver and renal insufficiency and cirrhosis. When all of these disease are unlikely, perform a diagnostic treatment toward heart failure (diuretic, cardiotonic agents), and if the treatment succeeds, the diagnosis of heart failure could be formed. When the serum BNP follows between 100pg/ml and 400pg/ml, the diagnosis of HF should be considered together with the clinical status, in which situation, Light s criteria could help diagnose HF. Light et al recommended a diagnostic procedure for patients with pleural effusion which suggested that the first step is to differentiate between transudation and exudation based on Light's criteria (23). If the pleural effusion meets exudative criteria, but the patient appears clinically to have a transudative effusion, then the serum-pleural fluid albumin gradient should be measured. Based our and other s study (24, 26), we recommended that for patients with bilateral effusion, the serum BNP should be taken first. If the serum BNP levels are above 400 pg/ml, the origin of bilateral pleural effusion should be HF. For patients whose serum BNP is in the gray area, we should make a thoracentesis and then follows the diagnostic procedure recommended by Light et al (22). The diagnostic thoracentesis could be performed on one side, unless there is a specific clinical indication (27) because the natures of both sides tend to be the same(28). If the pleural effusion is transudative, after excluding hypoalbuminemia, liver and renal insufficiency, and cirrhosis (22,23), we can give the treatment against HF, for patients whose pleural effusion are exudative, if pneumonia, cancer, tuberculosis (TB), and rheumatoid arthritis (RA), are excluded, small dose of diuretics and cardiotonic agents can be given. If the treatment against HF succeeds, the diagnosis of HF can be formed. If the serum BNP<100 pg/ml, especially when the Light s criteria is positive, HF can be excluded (Figure 2). Overall, in this study, we showed that combined use of serum BNP and Light s criteria could help in establishing or excluding the diagnosis of HF more effectively in patients with bilateral pleural effusion. The workup of patients with bilateral pleural effusion could be streamlined by obtaining serum BNP as an initial test, particularly in cases when HF related bilateral pleural effusion is suspected. References 1) Bui AL, Horwich TB, Fonarow GC. Epidemiology and risk profile of heart failure. Nat Rev Cardiol : ) Joung BY, Park BE, Kim DS, Hong BK, Kim DY, et al. B-type natriuretic Peptide predicts clinical presentations and ventricular overloading in patients with heart failure. Yonsei Med J :

5 The diagnostic value of BNP and Light s criteria on heart failure in patients with bilateral pleural effusion ) Gegenhuber A, Mueller T, Dieplinger B, Lenz K, Poelz W, et al. Plasma B-type natriuretic peptide in patients with pleural effusions: preliminary observations. Chest : ) Mark PB, Stewart GA, Gansevoort RT, Petrie CJ, McDonagh TA, et al. Diagnostic potential of circulating natriuretic peptides in chronic kidney disease. Nephrol Dial Transplant : ) McMurray JJ, Adamopoulos S, Anker SD, Auricchio A, Bohm M, et al. ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure 2012: The Task Force for the Diagnosis and Treatment of Acute and Chronic Heart Failure 2012 of the European Society of Cardiology. Developed in collaboration with the Heart Failure Association (HFA) of the ESC. Eur Heart J : ) O'Gara PT, Kushner FG, Ascheim DD, Casey DE Jr, Chung MK, et al ACCF/AHA guideline for the management of ST-elevation myocardial infarction: executive summary: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. Circulation : ) Weinfeld MS, Chertow GM, Stevenson LW. Aggravated renal dysfunction during intensive therapy for advanced chronic heart failure. Am Heart J : ) Light RW, Macgregor MI, Luchsinger PC, Ball WC Jr. Pleural effusions: the diagnostic separation of transudates and exudates. Ann Intern Med : ) Burgess LJ, Maritz FJ, Taljaard JJ. Comparative analysis of the biochemical parameters used to distinguish between pleural transudates and exudates. Chest : ) Shinto RA, Light RW. Effects of diuresis on the characteristics of pleural fluid in patients with congestive heart failure. Am J Med : ) Mahmood SS, Wang TJ. The epidemiology of congestive heart failure: the Framingham Heart Study perspective. Glob Heart : ) Maisel A, Mueller C, Adams K Jr, Anker SD, Aspromonte N, et al. State of the art: using natriuretic peptide levels in clinical practice. Eur J Heart Fail : ) Puchalski JT, Argento AC, Murphy TE, Araujo KL, Oliva IB, et al. Etiologies of bilateral pleural effusions. Respir Med : ) de Lemos JA, McGuire DK, Drazner MH. B-type natriuretic peptide in cardiovascular disease. Lancet : ) Morrow DA, de Lemos JA, Blazing MA, Sabatine MS, Murphy SA, et al. Prognostic value of serial B-type natriuretic peptide testing during follow-up of patients with unstable coronary artery disease. JAMA : ) Maisel A. B-type natriuretic peptide measurements in diagnosing congestive heart failure in the dyspneic emergency department patient. Rev Cardiovasc Med Suppl 4: S ) Pfisterer M, Buser P, Rickli H, Gutmann M, Erne P, et al. BNP-guided vs symptom-guided heart failure therapy: the Trial of Intensified vs Standard Medical Therapy in Elderly Patients With Congestive Heart Failure (TIME-CHF) randomized trial. JAMA : ) Porapakkham P, Porapakkham P, Zimmet H, Billah B, Krum H. B-type natriuretic peptide-guided heart failure therapy: A meta-analysis. Arch Intern Med : ) Komiya K, Ishii H, Murakami J, Yamamoto H, Okada F, et al. Relationship between CT findings and the plasma levels of brain natriuretic peptide in 29 patients with acute cardiogenic pulmonary edema. Acad Radiol : ) Light RW. The Light criteria: the beginning and why they are useful 40 years later. Clin Chest Med : ) Porcel JM. Pleural effusions from congestive heart failure. Semin Respir Crit Care Med : ) Light RW. Diagnostic principles in pleural disease. Eur Respir J : ) Bielsa S, Porcel JM, Castellote J, Mas E, Esquerda A, et al. Solving the Light s criteria misclassification rate of cardiac and hepatic transudates. Respirology : ) Farias AQ, Silvestre OM, Garcia-Tsao G, da CSLF, de Campos Mazo DF, et al. Serum B-type natriuretic peptide in the initial workup of patients with new onset ascites: a diagnostic accuracy study. Hepatology : ) Porcel JM, Martinez-Alonso M, Cao G, Bielsa S, Sopena A, et al. Biomarkers of heart failure in pleural fluid. Chest : ) Manzano-Fernandez S, Januzzi JL, Boronat-Garcia M, Pastor P, Albaladejo-Oton MD, et al. Impact of kidney dysfunction on plasma and urinary N-terminal pro-btype natriuretic peptide in patients with acute heart failure. Congest Heart Fail : ) Light RW. Use of pleural fluid N-terminal-pro-brain natriuretic peptide and brain natriuretic peptide in diagnosing pleural effusion due to congestive heart failure. Chest : ) Kalomenidis I, Rodriguez M, Barnette R, Gupta R, Hawthorne M, et al. Patient with bilateral pleural effusion: are the findings the same in each fluid. Chest : We thanked Department of Clinical Laboratory Department of Zhongnan hospital and Medical Record Department of Zhongnan hospital for their assisting in obtaining the laboratory and clinical data of patients. Corresponding author JIONG YANG The Second Clinical Medicine College of Wuhan University, No. 169, East Lake Road Wuchang district, Wuhan Hubei, (China)

Natriuretic Peptides The Cardiologists View. Christopher defilippi, MD University of Maryland Baltimore, MD, USA

Natriuretic Peptides The Cardiologists View Christopher defilippi, MD University of Maryland Baltimore, MD, USA Disclosures Research support: Alere, BG Medicine, Critical Diagnostics, Roche Diagnostics,