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 endothel in-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 endoth elin-1 in severe heart failure is primarily related to the precursor ' 'big'' endothelin-1, increased big endothelin-1 levels may be associat ed,vith a poor prognosis. Methods. Plasma big endothelin-1 concentrati ons, in addition to 16 clinical, hemodynamic and neurohumoral variable s, were obtained from 113 patients (mean age [+/-SEM] 53 +/- 1 years) with left ventricular ejection fraction <20% and were related to 1-yea r mortality by a stepwise Cox regression multivariate analysis. Result s. Plasma big endothelin-1 concentrations were significantly higher in patients with moderate and severe heart failure than in those with mi ld 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 furosem ide dose, left ventricular ejection fraction, most hemodynamic variabl es and plasma atrial natriuretic peptide, sodium renin activity and al dosterone levels were all related to mortality, but only functional cl ass provided additional prognostic information when big endothelin-1 p lasma levels were entered into the multivariate model. Conclusions. In advanced heart failure, plasma big endothelin-1 is strongly related t o survival and appears to predict 1-year mortality better than hemodyn amic variables and levels of atrial natriuretic peptide, an establishe d neurohumoral prognostic marker in chronic heart failure.