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.

Background: Glomerular filtration rate (GFR) has major prognostic implications in heart failure. Our objective was to validate the MDRD prediction equations for GFR in patients with advanced heart failure, and to compare their predictive performance to that of the CockcroftGault (CG) equation. Methods: We analysed GFR in 45 patients referred for heart transplantation evaluation.51 Cr -EDTA-measured GFR was compared to GFR estimates obtained by MDRD1 and MDRD2 equations, CG equation using actual body weight, and ideal body weight. Regression analyses and Pearson correlations were performed, and Bland and Altman plots were drawn. ROC curves were obtained to illustrate each equation's ability to predict a GFR less than 60 ml/min/1.73 m 2 (moderate renal impairment). Results: Patients had a mean age of 52 years, and 69% were in NYHA class III. The mean EDTA-measured GFR was 46.9 T 17.2 ml/min/ 1.73 m 2 . The MDRD1 equation provided the best predictive model (narrowest limits of agreement; r = 0.766, p < 0.001), and the highest performance in predicting a GFR less than 60 ml/min/1.73 m 2 (area under curve: 0.901). Conclusions: MDRD equations, especially MDRD1, adequately predict GFR in advanced heart failure, with higher accuracy than the CG equation. MDRD1 also has higher performance in predicting a GFR less than 60 ml/min/1.73 m 2 .

AimsApelin, a novel peptide with a putative role in cardiovascular homeostasis, has gained interest as an endogenous inotrope, but has yet to be described following acute myocardial infarction (AMI) in man. We aimed to characterize plasma apelin concentrations following AMI and to examine its relationship with clinical and prognostic biomarkers. Methods and resultsPlasma concentrations of apelin, N-terminal probrain natriuretic peptide (NT-proBNP), norepinephrine, and arginine vasopressin were measured in 100 patients [mean age 58.9 + 12 (SD) years, 77% male] admitted with AMI, with echocardiographic left ventricular (LV) ejection fraction ,40%, at mean 46 h after admission and at 24 weeks. Cardiac magnetic resonance imaging was performed pre-discharge and at 24 weeks. Thirty-eight subjects with no cardiac history acted as controls. Apelin concentration was reduced early after AMI (0.54 + 0.25 vs. 3.22 + 3.01 ng/mL, P ,0.001) and remained low at 24 weeks, although it did increase significantly from baseline to 0.62 + 0.36 ng/mL, P ¼ 0.030. Apelin had no relationship with any parameter of LV function over time. A relationship was found between baseline apelin and norepinephrine (r ¼ 0.26, P ¼ 0.008). Both NT-proBNP and norepinephrine correlated with adverse ventricular function after AMI. ConclusionPlasma apelin concentration is reduced early after AMI, increases significantly over time, but remains depressed at 24 weeks.--

NT-proBNP appears superior to GFR estimated by MDRD in patients with advanced CHF. Moreover, NT-proBNP was able to identify patients with a poor prognosis whose GFR was already low.

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 NTproBNP 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 NTproBNP concentration above the median and an absolute increase in NT-proBNP were independent predictors of mortality (χ 2 = 53, p < 0.0001 and χ 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.