Elevated plasma endothelin-1 is related to low natriuresis, clinical signs of congestion, and poor outcome in acute heart failure

Abstract

Aims: Endothelin-1 (ET-1) is a potent vasoconstrictor, which regulates renal and vascular function. We aimed to relate plasma levels of ET-1 with the clinical picture and outcomes in acute heart failure (AHF). Methods and results: We studied 113 patients with AHF [mean age 65 ± 13 (years), median (upper and lower quartiles) N-terminal pro-B-type natriuretic peptide, 5422 (2689; 8582) (pg/mL)], in whom plasma levels of ET-1 were serially measured at admission (10.8 ± 5.2), Day 1 (9.5 ± 3.4), and Day 2 (8.9 ± 3.8) (pg/mL). The population was divided into tertiles across baseline ET-1 levels. Patients in the highest ET-1 tertile had predominant clinical signs of peripheral congestion; however, no difference was observed in pulmonary congestion and severity of dyspnoea. They also presented lower spot urine sodium at admission (75 ± 35 vs. 99 ± 43 vs. 108 ± 30), 6 h (84 ± 34 vs. 106 ± 43 vs. 106 ± 35), and Day 1 (75 ± 38 vs. 96 ± 36 vs. 100 ± 35) (mmol/L), when compared with the second and first tertile, respectively (all P < 0.05); furthermore, they received higher doses of intravenous furosemide from Day 2 and had longer intravenous diuretics, as median switch to oral furosemide was 4 (3; 4) vs. 3 (2; 4) vs. 2 (2; 3) (days), respectively, P < 0.05. There was no difference in serum creatinine, urea, and renal injury biomarkers (kidney injury molecule-1, serum cystatin C, and urine neutrophil gelatinase-associated lipocalin) between the ET-1 tertiles. Higher values of ET-1 measured at each time point were related with a higher risk of 1 year mortality. Conclusions: Elevation of ET-1 is related to clinical signs of peripheral congestion, low urine sodium excretion, and poor outcome in AHF.