Biologic markers in acute heart failure

The major source of plasma BNP is the cardiac ventricles. This is unlike ANP, whose major storage sites include both the atria and ventricles.3 Unlike ANP, which is mainly released from its storage granules in response to atrial wall tension, BNP (as the nucleic acid sequence of the preproBNP gene with high turnover of messenger RNA [mRNA] suggests) is synthesized in bursts by increased gene expression owing to stretch stimulus to the ventricular wall as preproBNP (132 amino acids) and then released in direct proportion to ventricular volume expansion and pressure overload from ventricular myocytes as a 76 amino acid N-terminal fragment (NT-BNP) and a 32 amino acid active hormone (BNP)1, 4, 5 Since ANP is stored in granules and released episodically, a minor stimulus, like exercise, can trigger the release of significant amounts of ANP into the bloodstream.6 In contrast, BNP levels show only minor changes with vigorous exercise, making it unlikely that a normal patient would be classified as having congestive heart failure (CHF) based on a BNP level obtained after activity.7 This suggests that BNP may be a more sensitive and specific indicator of ventricular disorders than other natriuretic peptides.8 BNP levels accurately reflect the decompensated state of circulatory congestion.9 BNP has been found to be an independent predictor of high left ventricular end-diastolic pressure (LVEDP) and is more useful than ANP or other neurohormones for assessing mortality in patients with chronic CHF.9 The half-life of BNP is 22 minutes, and prior studies have established that BNP can accurately reflect pulmonary capillary wedge pressure (PCWP) changes every 2 hours.10, 11 B-type natriuretic peptide in the diagnosis of heart failure Shortness of breath is one of the most common presenting complaints to acute care settings. The presence of other comorbidities, such as chronic obstructive pulmonary disease (COPD), and the variability in physical findings of heart failure can led to substantial difficulties in making a definitive diagnosis in such patients. This clinical dilemma has led to substantial enthusiasm for BNP as an aid in the evaluation of patients presenting with unexplained dyspnea. In an initial study evaluating the role of BNP measurement in patients with unexplained dyspnea, Dao et al. found that BNP was a powerful predictor of a final diagnosis of heart failure (as determined by two cardiologists blinded to BNP results), with a plasma concentration of < 80 pg/mL having a negative predictive value of 98%.12 A larger, multicenter prospective study using similar methodology, the Breathing Not Properly (BNP) Multinational study, confirmed the substantial value of BNP as an adjunct to the diagnosis of heart failure, and identified 100 pg/mL as the cut-off that maximized sensitivity and specificity based on receiver operator characteristic (ROC) curves.13 Similar diagnostic utility of natriuretic peptide measurements have been demonstrated for levels of the inactive NT-BNP fragment, although optimal cut-off values differ for different assays.14 Data from the Breathing Not Properly study suggest that BNP is more useful than other elements of the clinical evaluation in establishing a diagnosis of heart failure, but is most effective when combined with other components of the evaluation.15 Recent data have also suggested that incorporation of BNP measurements into a diagnostic strategy may result in a significant reduction in health care costs.16.

Duke Scholars

Author Gary Michael Felker Medicine, Cardiology

Author Adrian Felipe Hernandez Medicine, Cardiology