Natriuretic peptides in the diagnosis and management of chronic heart failure

Abstract

Circulating levels of the BNP system can help in the diagnosis of cardiovascular disease and provide prognostic information not only for patients who have HF but also for the general population and other patient groups. Changes over time also carry prognostic information, and studies are assessing BNP-guided treatment strategies. With the identification of circulating molecular forms of BNP, new insights regarding the biology of the BNP system are emerging that may improve the diagnostic and prognostic value of BNP. Likewise, accounting for rs198389 (a common single nucleotide polymorphism that increases BNP levels) may help to further refine the use of components of the BNP system as biomarkers.

Figure 1

Schematic of proBNP and its processing to NTproBNP and BNP 1-32 by the protease corin, and processing of BNP 1-32 to BNP 3-32 by dipeptidyl peptidase IV.

Figure 2

Receiver operating characteristic curves of NTproBNP and BNP for detecting an ejection fraction of ≤40% in a random sample of the general population ≥45 years of Olmsted County, MN, USA. (A) for the entire population, (B) for patients ≥65 years, (C) for male subjects, and (D) for female subjects. AUC, area under the curve, EF, ejection fraction. From Costello-Boerrigter LC, Boerrigter G, Redfield MM, et al: Amino-terminal pro-B-type natriuretic peptide and B-type natriuretic peptide in the general community: determinants and detection of left ventricular dysfunction. J Am Coll Cardiol 2006;47(2):349, with permission.

Figure 3

Kaplan-Meier curves showing the cumulative incidence of death or hospital re-admission according to pre-discharge BNP ranges in patients hospitalized for decompensated heart failure; p<0.001 for trend among BNP ranges. Hazard ratios are shown on the right. From Logeart D, Thabut G, Jourdain P, et al: Predischarge B-type natriuretic peptide assay for identifying patients at high risk of re-admission after decompensated heart failure. J Am Coll Cardiol 2004;43(4):639, with permission.

Figure 4

Hazard ratios for risk of death/cardiac transplantation in ambulatory patients with heart failure. Time dependent multivariate model with serial follow-up troponin T and BNP values (every 3 months). + indicates elevated BNP or troponin T ≥0.01 ng/mL or >0.03 ng/mL; - not elevated (HR, 1.0 for elevation of neither BNP or troponin T). From Miller WL, Hartman KA, Burritt MF, et al: Serial biomarker measurements in ambulatory patients with chronic heart failure: the importance of change over time. Circulation 2007;116(3):254, with permission.

Figure 5

Cardiac-related event risks associated with changes in BNP concentration (A) and NTproBNP concentrations (B) in ambulatory patients with heart failure. Hazard ratios (95% confidence interval) from Cox models relative to no changes in BNP or NTproBNP or no crossing over from more than to less than the BNP (500 ng/L) or NTproBNP (1000 ng/L) cutpoint values. Tx, transplantation. From Miller WL, Hartman KA, Grill DE, et al: Only large reductions in concentrations of natriuretic peptides (BNP and NT-proBNP) are associated with improved outcome in ambulatory patients with chronic heart failure. Clin Chem 2008(1):81, with permission.

Figure 5

Cardiac-related event risks associated with changes in BNP concentration (A) and NTproBNP concentrations (B) in ambulatory patients with heart failure. Hazard ratios (95% confidence interval) from Cox models relative to no changes in BNP or NTproBNP or no crossing over from more than to less than the BNP (500 ng/L) or NTproBNP (1000 ng/L) cutpoint values. Tx, transplantation. From Miller WL, Hartman KA, Grill DE, et al: Only large reductions in concentrations of natriuretic peptides (BNP and NT-proBNP) are associated with improved outcome in ambulatory patients with chronic heart failure. Clin Chem 2008(1):81, with permission.

Figure 6

Kaplan-Meier event curves for time to heart failure event or death in heart failure patients randomized to a NTproBNP guided group or a clinical (control) group. From Troughton RW, Frampton CM, Yandle TG, et al: Treatment of heart failure guided by plasma aminoterminal brain natriuretic peptide (N-BNP) concentrations. Lancet 2000;355(9210):1128, with permission.