Do plasma concentrations of apelin predict prognosis in patients with advanced heart failure?

AIM: Apelin is an endogenous vasodilator and inotrope, plasma concentrations of which are reduced in advanced heart failure (HF). We determined the prognostic significance of plasma concentrations of apelin in advanced HF. PATIENTS & METHODS: Plasma concentrations of apelin were measured in 182 patients with advanced HF secondary to left ventricular systolic dysfunction. The predictive value of apelin for the primary end point of all-cause mortality was assessed over a median follow-up period of 544 (IQR: 196-923) days. RESULTS: In total, 30 patients (17%) reached the primary end point. Of those patients with a plasma apelin concentration above the median, 14 (16%) reached the primary end point compared with 16 (17%) of those with plasma apelin levels below the median (p = NS). NT-proBNP was the most powerful prognostic marker in this population (log rank statistic: 10.37; p = 0.001). CONCLUSION: Plasma apelin concentrations do not predict medium to long-term prognosis in patients with advanced HF secondary to left ventricular systolic dysfunction.

Renal dysfunction, as measured by the modification of diet in renal disease equations, and outcome in patients with advanced heart failure.

AIMS: This study evaluates the prognostic utility of renal dysfunction estimated by the recently validated modification of diet in renal disease (MDRD) equations and compares it with the currently most promising predictor of prognosis in patients with advanced heart failure. METHODS AND RESULTS: We prospectively studied 182 consecutive patients with advanced chronic heart failure (CHF) referred for consideration of cardiac transplantation, with a median follow-up of 642 days. Glomerular filtration rate (GFR) was estimated using the MDRD equations and plasma taken for NT-proBNP analysis. The primary endpoint of all-cause mortality was reached in 40 patients (13.2% crude 1-year mortality), and the combined secondary endpoint of all-cause mortality or urgent CTx was reached in 44 patients. The mean GFR estimated by MDRD-1 was 58 mL/min/1.73 m(2). The median NT-proBNP concentration was 1505 (517-4014) pg/mL. Although GFR estimated by MDRD-1 was a univariate marker of all-cause mortality, the only predictor of either endpoint independent of other variables was an NT-proBNP concentration above the median. CONCLUSION: 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.

Can we use B-type natriuretic peptides to monitor patients with heart failure?

The B-type natriuretic peptides (BNPs) now have a well-established role in the diagnosis of heart failure. There is also a wealth of evidence on their ability as prognostic markers in patients with heart failure. The other potential role of BNPs is in the arena of therapy monitoring, although much less is known regarding this putative application. This review summarizes what evidence there is both for and against using BNPs to monitor heart failure patients.

B-type natriuretic peptides in heart failure.

There is increasing interest in the B-type natriuretic peptides in many clinical settings, with most research centered on patients with heart failure. These peptides have a strong negative predictive value in patients suspected of having this diagnosis, but are also known to be powerfully predictive of an adverse outcome. This latter property is particularly important in patients with advanced heart failure, allowing the selection of at-risk individuals for therapies that are in scarce resource. There is also ongoing research into B-type natriuretic peptide as a treatment for decompensated heart failure, as well as in other clinical contexts. This review aims to summarize the contemporary and established data on the B-type natriuretic peptides, with particular emphasis in the context of advanced heart failure.

Emerging role of the apelin system in cardiovascular homeostasis.

The angiotensin receptor-like 1 (APJ) and its novel ligand, apelin, share similarities in structure and anatomical distribution with that of angiotensin II and the angiotensin II type 1 receptor. However, apelin has positive inotropic, vasodilatory and diuretic properties. Differential expression and synthesis of apelin and the APJ receptor in normal and failing hearts suggest that the apelin system may contribute to the pathophysiology of human heart failure and has potential therapeutic use in treatment of heart failure.

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.

The Modification of Diet in Renal Disease (MDRD) equations provide valid estimations of glomerular filtration rates in patients with advanced heart failure.

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 Cockcroft-Gault (CG) equation. METHODS: We analysed GFR in 45 patients referred for heart transplantation evaluation. 51Cr-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 m2 (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+/-17.2 ml/min/1.73 m2. 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 m2 (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 m2.

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.