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Prognostic impact of big endothelin-1 plasma concentrations compared with invasive hemodynamic evaluation in severe
R Pacher1, B Stanek, M Hülsmann
1Department of Cardiology, University of Vienna, Austria.
Insights
In advanced heart failure, elevated big endothelin-1 plasma levels indicate a poor prognosis. This biomarker predicts one-year mortality better than traditional hemodynamic measures.
Area of Science:
- Cardiology
- Biomarkers
- Prognostic Markers
Background:
- Heart failure is associated with increased endothelin-1 production.
- Elevated big endothelin-1, the precursor to endothelin-1, may signal a poor prognosis in severe heart failure.
Purpose of the Study:
- To investigate the relationship between plasma big endothelin-1 levels and survival in advanced heart failure.
- To determine if big endothelin-1 is a better predictor of mortality than established prognostic markers.
Main Methods:
- Plasma big endothelin-1 concentrations were measured in 113 patients with advanced heart failure (left ventricular ejection fraction <20%).
- Patients' data were analyzed using stepwise Cox regression to assess 1-year mortality.
- 16 clinical, hemodynamic, and neurohumoral variables were also assessed.
Main Results:
- Plasma big endothelin-1 levels were significantly higher in patients with moderate to severe heart failure compared to mild heart failure.
- Non-survivors had significantly higher big endothelin-1 levels than survivors.
- Big endothelin-1 levels were strongly associated with 1-year mortality (p < 0.0001).
Conclusions:
- Plasma big endothelin-1 is a strong predictor of survival in advanced heart failure.
- Big endothelin-1 appears to be a more potent prognostic marker than hemodynamic variables and atrial natriuretic peptide.
Objectives:
This study sought to test the hypothesis that big endothelin-1 plasma levels in advanced heart failure are related to survival.
Background:
In heart failure, production of the potent vasoconstrictor endothelin-1 is increased. Because elevation of immunoreactive endothelin-1 in severe heart failure is primarily related to the precursor "big" endothelin-1, increased big endothelin-1 levels may be associated with a poor prognosis.
Methods:
Plasma big endothelin-1 concentrations, in addition to 16 clinical, hemodynamic and neurohumoral variables, were obtained from 113 patients (mean age -=/[SEM] 53 +/- 1 years) with left ventricular ejection fraction <20% and were related to 1-year mortality by a stepwise Cox regression multivariate analysis.
Results:
Plasma big endothelin-1 concentrations were significantly higher in patients with moderate and severe heart failure than in those with mild heart failure (4.5 +/- 0.4 and 6.0 +/- 0.1 vs. 2.7 +/- 0.1 fmol/ml, p = 0.0001, respectively) and lower in 58 one-year survivors than in 29 nonsurvivors (2.6 +/- 0.1 vs. 5.9 +/- .04 fmol/ml, p = 0.0001) and 26 heart transplant recipients. By univariate analysis, big endothelin-1 plasma concentrations (p < 0.0001), functional class, daily furosemide dose, left ventricular ejection fraction, most hemodynamic variables and plasma atrial natriuretic peptide, sodium renin activity and aldosterone levels were all related to mortality, but only functional class provided additional prognostic information when big endothelin-1 plasma levels were entered into the multivariate model.
Conclusions:
In advanced heart failure, plasma big endothelin-1 is strongly related to survival and appears to predict 1-year mortality better than hemodynamic variables and levels of atrial natriuretic peptide, an established neurohumoral prognostic marker in chronic heart failure.