Prognostic impact of big endothelin-1 plasma concentrations compared with invasive hemodynamic evaluation in severe heart failure

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,vith 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 +/- 0.4 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.