Big ET for the diagnosis of HFpEF

Renal dysfunction may limit the clinical application of NT-proBNP in the diagnosis of heart failure.

Big ET is an excellent biomarker candidate for the diagnosis of HFpEF in CKD, independent of GFR 

This was recently discussed in: Renal function, N-terminal Pro-B-Type natriuretic peptide, propeptide big-endothelin and patients with heart failure and preserved ejection fraction.

Ingrid Gergei, Bernhard K. Krämer, Hubert Scharnagl, Tatjana Stojakovic, Winfried März. Peptides. 2018 Apr 21. pii: S0196-9781(18)30071-8. Click link for abstract.

Highlights:

• NT-proBNP is strongly associated with GFR and shows an exponential negative correlation with GFR decline.
• Big ET-1 is much less affected by GFR decline than NT-proBNP
• A single cut-off point is sufficient in the diagnosis of HFpEF in CKD, independent of GFR

Big ET for the diagnosis of HFpEF

The Biomedica Big Endothelin ELISA Assay is:

• EASY – can be used in every lab
• ROBUST & fully VALIDATED
• CE registered – for IVD use in EU
• GOOD ANALYTE STABILITY in serum and plasma

Related publications

Prognostic value of plasma big endothelin-1 in left ventricular non-compaction cardiomyopathy.

Fan P, Zhang Y, Lu YT, Yang KQ, Lu PP, Zhang QY, Luo F, Lin YH, Zhou XL, Tian T. Heart. 2021. 107(10):836-841. PMID: 33055147; PMCID: PMC8077223.

Abstract

Objective: To determine the prognostic role of big endothelin-1 (ET-1) in left ventricular non-compaction cardiomyopathy (LVNC).

Methods: We prospectively enrolled patients whose LVNC was diagnosed by cardiac MRI and who had big ET-1 data available. Primary end point was a composite of all-cause mortality, heart transplantation, sustained ventricular tachycardia/fibrillation and implanted cardioverter defibrillator discharge. Secondary end point was cardiac death or heart transplantation.

Results: Altogether, 203 patients (median age 44 years; 70.9% male) were divided into high-level (≥0.42 pmol/L) and low-level (<0.42 pmol/L) big ET-1 groups according to the median value of plasma big ET-1 levels. Ln big ET-1 was positively associated with Ln N-terminal pro-brain natriuretic peptide, left ventricular diameter, but negatively related to age and Ln left ventricular ejection fraction. Median follow-up was 1.9 years (IQR 0.9-3.1 years). Kaplan-Meier analysis showed that, compared with patients with low levels of big ET-1, those with high levels were at greater risk for meeting both primary (p<0.001) and secondary (p<0.001) end points. The C-statistic estimation of Ln big ET-1 for predicting the primary outcome was 0.755 (95% CI 0.685 to 0.824, p<0.001). After adjusting for confounding factors, Ln big ET-1 was identified as an independent predictor of the composite primary outcome (HR 1.83, 95% CI 1.27 to 2.62, p=0.001) and secondary outcome (HR 1.93, 95% CI 1.32 to 2.83, p=0.001).

The big ET-1 concentrations were quantified using the Big Endothelin-1 ELISA Kit (NO. BI-20082H; Biomedica, Wien, Austria.

Related publications

 

Plasma Endothelin-1 and Risk of Death and Hospitalization in Patients Undergoing Maintenance Hemodialysis.

Li P, Schmidt IM, Sabbisetti V, Tio MC, Opotowsky AR, Waikar SS. Clin J Am Soc Nephrol. 2020. 8;15(6):784-793. PMID: 32381583.

Abstract

Background and objectives: Endothelin-1 is a potent endothelium-derived vasoconstrictor peptide implicated in the pathogenesis of hypertension, congestive heart failure, and inflammation, all of which are critical pathophysiologic features of CKD.

Design, setting, participants, & measurements: To test the hypothesis that plasma endothelin-1 levels are associated with increased risks of mortality and hospitalization in patients with chronic kidney failure, we measured plasma endothelin-1 levels in a prospective cohort of 794 individuals receiving maintenance hemodialysis. The primary outcomes were time to death and time to hospitalization.

Results: The median plasma endothelin-1 level was 2.02 (interquartile range, 1.57-2.71) pg/ml. During a median follow-up period of 28 (interquartile range, 21-29) months, 253 individuals (32%) died and 643 individuals (81%) were hospitalized at least once. In multivariable models adjusted for demographic, clinical, and laboratory variables, individuals in the highest quartile of plasma endothelin-1 had a 2.44-fold higher risk of death (hazard ratio, 2.44; 95% confidence interval, 1.61 to 3.70) and a 1.54-fold higher risk of hospitalization (hazard ratio, 1.54; 95% confidence interval, 1.19 to 1.99) compared with individuals in the lowest quartile. The Harrell C-statistic of the fully adjusted model increased from 0.73 to 0.74 after addition of natural log-transformed plasma endothelin-1 (P<0.001) for all-cause mortality, and increased from 0.608 to 0.614 after addition of natural log-transformed plasma endothelin-1 (P=0.002) for hospitalization.

Conclusions: Higher plasma endothelin-1 is associated with adverse clinical events in patients receiving hemodialysis independent of previously described risk factors.

Podcast: This article contains a podcast at https://www.asn-online.org/media/podcast/CJASN/2020_05_15_CJN11130919.mp3.

Keywords: Chronic; Cohort Studies; Endothelin-1; Endothelins; Inflammation; Kidney Failure; Prospective Studies; Renal Insufficiency; Vasoconstrictor Agents; cardiovascular disease; dialysis; endothelium; heart failure; hemodialysis; hospitalization; hypertension; mortality; risk factors.