A change in N-terminal pro-brain natriuretic peptide is predictive of outcome in patients with advanced heart failure.

BACKGROUND: The prognosis of chronic heart failure has improved with modern medical therapy. However, identifying those patients who fail to respond to such therapy and therefore those who remain at high risk is notoriously difficult. The B-type natriuretic peptides are established independent predictors of prognosis in CHF. However, the relevance of a change in NT-proBNP concentration over time in advanced heart failure is unknown. METHODS: We prospectively studied 133 patients with advanced CHF referred for consideration of cardiac transplantation. Plasma for NT-proBNP analysis was sampled at baseline and a median of 4 months later in the 112 patients surviving without cardiac transplantation. Patients were followed up for a median of 1003 days. RESULTS: The primary endpoint of all-cause mortality occurred in 30 (26.8%) patients. Those subjects who had the highest NT-proBNP concentration at 4 months were at the greatest risk of death (log rank statistic=10.4, p=0.001). On Cox regression analysis, both a NT-proBNP concentration above the median and an absolute increase in NT-proBNP were independent predictors of mortality (chi(2)=53, p<0.0001 and chi(2)=17.3, p<0.0001, respectively). CONCLUSION: A single NT-proBNP concentration above the median and a change in NT-proBNP concentration over a 4-month period were independent predictors of mortality in patients with advanced heart failure.

Plasma concentrations of the novel peptide apelin are decreased in patients with chronic heart failure.

BACKGROUND: Apelin, the novel endogenous ligand for the G-protein-coupled receptor APJ, has shown positive inotropic, vasodilatory and diuretic properties in animal studies. Differential expression and synthesis of apelin and APJ receptors have been observed in normal and failing human hearts, suggesting a possible role in cardiovascular homeostasis. Changes in plasma apelin concentrations in relation to heart failure have been described in small studies with conflicting results. Our aim was to evaluate plasma apelin concentrations in a large cohort of patients with chronic heart failure (CHF) across a broad spectrum of disease severity. METHOD AND RESULTS: Plasma apelin concentrations were measured in 202 patients with CHF secondary to left ventricular systolic dysfunction and 22 age-matched controls. Plasma apelin concentrations were significantly lower in patients with CHF, irrespective of NYHA class, ejection fraction or aetiology when compared to age-matched controls (0.85 [0.53-2.04] versus 3.76 [0.85-5.13] ng/ml, p<0.001). Apelin concentrations were correlated with peak VO(2) and right ventricular ejection fraction, but not with age, sex, body mass index, renal function or NT-proBNP concentrations. CONCLUSIONS: Plasma apelin concentrations are decreased in patients with CHF. The Apelin-APJ signaling pathway may be a potentially important mediator in the pathophysiological processes of heart failure and may therefore have potential therapeutic implications.

N-terminal brain natriuretic peptide, but not anemia, is a powerful predictor of mortality in advanced heart failure.

BACKGROUND: Anemia is prevalent in patients with chronic heart failure, the proportion of which increases with deteriorating New York Heart Association functional class. Anemia is also associated with increased symptoms, more frequent hospitalizations, and, in some studies, with an increased mortality rate. We have demonstrated that N-terminal brain natriuretic peptide (NT-proBNP) is a powerful predictor of death in advanced heart failure and is superior to the traditional markers of chronic heart failure (CHF) severity. However, to date, there are no published data that compare the prognostic ability of NT-proBNP with that of hemoglobin and hematocrit in patients with advanced heart failure who are referred for consideration of cardiac transplantation at a time when erythropoietin is under investigation as a treatment option in such a population. METHODS AND RESULTS: We prospectively studied 182 consecutive patients with advanced CHF who had been referred for consideration of cardiac transplantation. Blood samples were taken at recruitment for routine investigation and for NT-proBNP analysis; the patients' condition was followed for a median of 554 days. The primary end point of all-cause death was reached in 30 patients, and the secondary end point of all-cause death or urgent cardiac transplantation was reached in 34 patients. The mean hemoglobin level was 13.9 +/- 2.2 g/dL, and the median concentration of NT-proBNP was 1505 pg/mL (interquartile range, 517-4015). The only multivariate predictor of all-cause death (chi 2 = 14.2; P < .001) or the secondary end point of all-cause death or urgent transplantation (chi 2 = 21.8; P < .001) was an NT-proBNP concentration above the median value. CONCLUSION: A single measurement of NT-proBNP in patients with advanced CHF can help to identify patients who are at a higher risk of death and is a better prognostic marker than anemia.

Comparison of selective ET(A) and ET(B) receptor antagonists in patients with chronic heart failure.

BACKGROUND: The vasoconstrictor action of endothelin-1 (ET-1) is mediated through ET(A) and ET(B) receptor subtypes on vascular smooth muscle. ET(B) receptors are also present on the vascular endothelium where they mediate vasodilation. Animal studies suggest that the ET(B) receptor also acts as a clearance receptor for endothelin. AIMS: To investigate the effects of a selective ET(A) and a selective ET(B) receptor antagonist alone and in combination on haemodynamics and circulating concentrations of ET-1 in patients with chronic heart failure. RESULTS: Infusion of BQ-123 (n=10), a selective ET(A) receptor antagonist, led to systemic vasodilation and did not change plasma ET-1 concentrations (1.38+/-0.82 to 1.38+/-0.91 fmol/ml, ns). Infusion of BQ-788 (n=8) led to systemic vasoconstriction with a rise in plasma ET-1 (1.84+/-1.06 to 2.73+/-0.99 fmol/ml, p<0.01). The addition of BQ-123 to BQ-788 led to systemic and pulmonary vasodilation with no further increase in plasma ET-1 concentrations (2.80+/-1.14 to 2.90+/-1.20 fmol/ml, ns). CONCLUSION: The rise in plasma ET-1 concentrations in response to selective blockade of ET(B) receptors and the associated adverse haemodynamic effects suggest that ET(B) receptors have a role in the clearance of ET-1 in man and that their blockade may not be advantageous for patients with heart failure.

Multicenter analytical performance evaluation of the Elecsys proBNP assay.

The purpose of this multicenter study was to evaluate the technical performance of the automated Elecsys proBNP (brain natriuretic peptide) assay, which is indicated as an aid in the diagnosis of individuals suspected of having congestive heart failure. The Elecsys proBNP assay is an electrochemiluminescent immunoassay employing two polyclonal NT-proBNP-specific antibodies in a sandwich test format. The study was performed on the three Elecsys analyzers (E 1010, E 2010, and E 170) at eight different sites world-wide. Within- and total precision were < or = 3%, with total precision slightly higher on the Elecsys E 170 instrument with multiple modules. Reproducibility among sites and platforms was < 5%. Precision at particularly low NT-proBNP concentrations was assessed down to approximately 25 pg/ml with CVs of 12.6% at 29.2 pg/ml and 9.6% at 38.5 pg/ml for the Elecsys 1010/2010 and E 170, respectively. Linearity was evaluated up to 25,000 pg/ml with a sample-based non-linear response observed with recoveries of < 90% for proBNP concentrations < 10,000 pg/ml. Slopes ranged between 0.92 and 1.02 and intercepts from -5.3 to 10.4 pg/ml (r > or = 0.998) among the three types of analyzers. Slopes were 4.95 and 4.53 in comparison to the Biosite Triage and Shionogi BNP assays. There was no assay interference, and no effect of barrier gels, tube composition, or freeze-thaw. NT-proBNP concentrations in EDTA plasma were up to 10% lower than in serum or heparinized plasma and the analyte was stable at 4 degrees C for up to 72 hours (the maximum time tested). There was no circadian rhythm in normal subjects or congestive heart failure patients and there was no effect of drawing position. In summary, the Elecsys proBNP assay exhibits good technical performance and is suitable for use in routine clinical laboratories to aid in the diagnosis of congestive heart failure.