Elsevier

American Heart Journal

Volume 152, Issue 5, November 2006, Pages 828-834
American Heart Journal

Curriculum in Cardiology
Serial testing of B-type natriuretic peptide and NTpro-BNP for monitoring therapy of heart failure: The role of biologic variation in the interpretation of results

https://doi.org/10.1016/j.ahj.2006.08.021Get rights and content

Background

B-Type natriuretic peptide (BNP) and NTpro-BNP are widely used for diagnosis and risk stratification of patients with heart failure (HF). Although not currently cleared by the Food and Drug Administration as a test indication, there is interest in using these biomarkers for monitoring the success of HF medications. An assessment of the analytical and biologic variations is necessary to interpret the results of serial testing.

Methods and Results

The intra-individual biologic variances and analytical assay variances of BNP and NT-proBNP from healthy subjects and those with stable HF were reviewed. The analytical variability of BNP and NT-proBNP assays was reported, as some have suggested that only the analytical variance is important in interpreting the results of tightly regulated hormones. The reference change values (RCV) for serial measurements were derived and used to interpret results of therapeutic studies whereby serial changes in BNP and NT-proBNP concentrations were obtained to evaluate the therapeutic success of short-term (inpatient) and long-term (outpatient) management. The use of RCV may also be important in studies comparing BNP-guided versus physician-guided HF drug therapy.

Conclusions

Relative to the RCV, short-term therapeutic studies of inpatients have largely resulted in a statistically significant decline in BNP and NT-proBNP with clinical evidence of patient improvements. In contrast, many therapeutic studies involving long-term outpatient monitoring have produced changes in BNP/NT-proBNP that do not exceed the biologic variances. The value of BNP for monitoring therapeutic success can be questioned for trials that demonstrate clinical benefit without statistically significant decreases in biomarker levels.

Section snippets

Determination of biologic variability and reference change values for BNP and NT-proBNP

The biologic variation (BV) of a marker is important for the proper interpretation of serial test results.3 The derived values are the analytical (CVA), intra-individual (CVI), and inter-individual (CVG) variations. Studies are typically conducted on healthy individuals, although some investigators have reported values in stable patients with heart failure. Table I summarizes the BV studies for BNP and NT-proBNP.4, 5, 6 The CVA for automated BNP and NT-proBNP assays is considerably lower than

Inpatient monitoring of BNP/NT-proBNP for decompensated HF

There have been a few studies that have compared BNP and NT-proBNP concentrations before and after therapeutic management. Short-term inhospital management of patients with HF focuses on the reduction of natriuretic peptides as the result of compensating patients who are admitted with volume and fluid overloads. In the majority of the cases cited below, the investigators stated that the results of the BNP tests were blinded to those assessing the outcomes. There would be significant study

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