Background: In aortic stenosis, natriuretic peptides have recently been shown to correlate with ventricular function and to predict symptom-free survival and outcome. Elevated big endothelin-1 (bigET) is associated with poor prognosis in chronic heart failure, but little is known about its role in severe aortic stenosis.
Methods: In 61 patients with aortic stenosis (71+/-10 years, mean gradient 65+/-20 mm Hg, valve area 0.63+/-0.15 cm2), plasma bigET was determined by radioimmunoassay and related to echocardiographic parameters, symptoms and survival. Patients were followed for 1 year.
Results: BigET (mean 2.3+/-1.5, range 0.1-7.5 fmol/ml) was elevated > or = 1.9 fmol/ml in 54% of patients, but was not correlated to the transvalvular gradients or valve area. BigET did not differ significantly between 14 asymptomatic (2.4+/-1.0 fmol/ml) and 47 symptomatic patients (2.3+/-1.6 fmol/ml), although the highest levels were observed in 5 patients in NYHA class III-IV (4.2+/-2.2 fmol/ml, p=0.035). No significant difference in bigET was observed between 51 survivors and 10 patients who died during follow-up (2.2+/-1.4 vs 2.7+/-1.6 fmol/ml). BigET did not differ between 7 asymptomatic patients developing symptoms and those remaining asymptomatic during follow-up. BigET was significantly related to the systolic blood pressure and left ventricular systolic pressure (r=0.389, p=0.0025 and r=0.401, p=0.0018, respectively), but not to the diastolic blood pressure or interventricular septal wall thickness. BigET was inversely related to the left ventricular ejection fraction (r=0.327, p=0.01) and fractional shortening (r=0.391, p=0.044).
Conclusion: Although frequently elevated, bigET-1 is not a useful predictor of symptoms or outcome in patients with severe aortic stenosis. BigET increases inversely with left ventricular function and directly with systolic left ventricular and blood pressure, but is not related to transvalvular gradients or valve area.