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.

Distinct renin/aldosterone activity profiles correlate with renal function, natriuretic response, decongestive ability and prognosis in acute heart failure

“…In our study patients did not uniformly suffer from inability to excrete sodium, as those from RAAS − /− and RAAS +/+ profiles excreted urine with significantly higher sodium concentration during first 48 h of hospitalization, which has also translated into an average shorter hospital stay. This is in agreement with our previous report linking natriuresis with other vasoactive molecule (endothelin-1) in AHF [24].…”

Elevated Plasma Big Endothelin-1 at Admission Is Associated With Poor Short-Term Outcomes in Patients With Acute Decompensated Heart Failure

“…These findings revealed that the strong endothelin system activation reflected not only cardiac function but also renal and liver functions and personal nutritional status. The important biological functions of this comprehensive indicator in multiple organs were consistent with previous works ( 13 , 24 , 26 , 27 ).…”

Novel Biomarkers in Heart Failure: New Insight in Pathophysiology and Clinical Perspective

“…Baseline concentration of ET-1 was proportional to the severity of disease (in terms of NYHA class and LVEF) and it was revealed to be an independent outcome predictor of all-cause morbidity and mortality [44]. More recently, ET-1 role was also investigated in acute HF patients, and it was demonstrated that its concentration correlates with clinical signs of congestion (fluid overload), low natriuresis (i.e., urine sodium excretion), and, finally, that levels of ET-1 are also a significant prognostic factor of one-year mortality due to acute HF [46].…”