Serum B-type natriuretic peptide in the initial workup of patients with new onset ascites: A diagnostic accuracy study

Abstract

Heart failure (HF) is, after cirrhosis, the second-most common cause of ascites. Serum B-type natriuretic peptide (BNP) plays an important role in the diagnosis of HF. Therefore, we hypothesized that BNP would be useful in the differential diagnosis of ascites. Consecutive patients with new onset ascites were prospectively enrolled in this crosssectional study. All patients had measurements of serum-ascites albumin gradient (SAAG), total protein concentration in ascitic fluid, serum, and ascites BNP. We enrolled 218 consecutive patients with ascites resulting from HF (n 5 44), cirrhosis (n 5 162), peritoneal disease (n 5 10), and constrictive pericarditis (n 5 2). Compared to SAAG and/or total protein concentration in ascites, the test that best discriminated HF-related ascites from other causes of ascites was serum BNP. A cutoff of >364 pg/mL (sensitivity 98%, specificity 99%, and diagnostic accuracy 99%) had the highest positive likelihood ratio (168.1); that is, it was the best to rule in HF-related ascites. Conversely, a cutoff £ 182 pg/mL had the lowest negative likelihood ratio (0.0) and was the best to rule out HF-related ascites. These findings were confirmed in a 60-patient validation cohort. Conclusions: Serum BNP is more accurate than ascites analyses in the diagnosis of HFrelated ascites. The workup of patients with new onset ascites could be streamlined by obtaining serum BNP as an initial test and could forego the need for diagnostic paracentesis, particularly in cases where the cause of ascites is uncertain and/or could be the result of HF. (HEPATOLOGY 2014;59:1043-1051 See Editorial on Page 751A scites secondary to heart failure (HF) is, after cirrhosis, the second-most common cause of ascites. 1 The pathophysiology of ascites in both HF and cirrhosis is hepatic sinusoidal hypertension, and therefore the serum-ascites albumin gradient (SAAG) is greater than 1.1 g/dL in both conditions. 2 Because the hepatic sinusoids are normal (leaky, i.e., without significant collagen deposition in the space of Disse) in HF and are abnormal in cirrhosis (less leaky as a result of capillarization of sinusoids), 3 ascites total protein content is higher in HF-related ascites than in cirrhotic ascites and has been used to help in the differential diagnosis between these two entities, with a ascites protein level of >2.5 mg/dL suggesting the presence of ascites related to HF. However, a significant number of cases are still misclassified. 2,4 Even the Abbreviations: ASE, American Society of Echocardiography; BNP, B-type natriuretic peptide; CLD, chronic liver disease; HF, heart failure; HVPG, hepatic venous pressure gradient; INR, international normalized ratio; IQR, interquartile range; LR, likelihood ratio; NPV, negative predictive value; NT-proBNP, N-terminal proBNP; PH, portal hypertension; PPV, positive predictive value; SAAG, serum-ascites albumin gradient; STARD, Standards for reporting Studies of Diagnostic Accuracy; US, ultrasound.From the

Evaluation of New-Onset Ascites

“…5 This pattern occurs because hepatic sinusoids are normally permeable in heart failure–related ascites, which allows for leakage of protein-rich lymph into the abdominal cavity. 7,9 In cirrhosis, hepatic sinusoids are less permeable due to fibrous tissue deposition, resulting in ascites with low protein content. 7,9 Nevertheless, this patient likely also has some liver fibrosis due to long-standing congestive hepatopathy.…”

“…7,9 In cirrhosis, hepatic sinusoids are less permeable due to fibrous tissue deposition, resulting in ascites with low protein content. 7,9 Nevertheless, this patient likely also has some liver fibrosis due to long-standing congestive hepatopathy. Her anemia and thrombocytopenia are predominantly due to splenomegaly.…”

“…6 A recent study noted a combined SAAG level of 1.1 g/dL or greater and an ascites protein level of 2.5 g/dL or greater in a validation cohort had a diagnostic accuracy of 78.3% for heart failure–related ascites, with 53.3% sensitivity (95% CI, 28.1%–78.6%), 86.7% specificity (95% CI, 76.7%–96.6%), a negative likelihood ratio of 0.54, and a positive likelihood ratio of 4.00. 7 Supplementation with intravenous albumin may confound test results. The Medicare midpoint reimbursement is $10.31 for peritoneal fluid cell count with differential, $6.75 for peritoneal fluid protein, and $9.53 for peritoneal fluid albumin.…”

Ascitic fluid total protein, a useful marker in non‐portal hypertensive ascites

“…Rivalta test was developed in 1895 by the Italian physician Fabio Rivalta and is widely used as a marker for the differentiation between exudates and transudates in human body cavity effusions. 3,[8][9][10] Previous studies demonstrated that most cases of cardiac ascites with high AFTP (≥ 25 g/L) were incorrectly considered to have an AFTP less than 25 g/L. Previous study demonstrated that quantitative analysis of AFTP had diagnostic accuracy of 88%.…”

“…6,7 Samples are categorized as transudates, if the AFTP is less than 25 g/L and as exudates if AFTP is greater than 25 g/L. 3, 10 Gupta et al reported that 24% of patients with uncomplicated cirrhosis had an AFTP concentration greater than 25 g/L, 8 and Alexandrakis et al reported that 20% of malignant ascites had a low AFTP concentration (< 25 g/L). 8 Thus, some clinical practice guidelines recommend that AFTP concentration should be determined in the initial laboratory investigation of ascitic fluid.…”