Abstract 4332: Stable Precursor Fragments of Vasoactive Peptides Predict Outcome in Patients with Chronic Heart Failure. Data from the GISSI-Heart Failure Trial

Abstract

The clinical evaluation of several hormones directly involved in the pathophysiology of HF may be hindered by their instability, in particular when dealing with real-life multicenter studies. We assessed the prognostic performance of their stable precursor fragments in patients with chronic HF. Stable fragments of the precursors of atrial natriuretic peptide (mid-regional MR-proANP), endothelin-1 (C-terminal CT-proET-1), adrenomedullin (MR-proADM) and vasopressin (CT-proAVP) were measured at baseline (immunoassays BRAHMS) in 1237 patients with chronic HF enrolled in the multicenter GISSI-HF trial (80.4% males, age 66±11 y, NYHA III-IV 26%, 88% with LVEF<0.40). Association between markers and all-cause mortality (follow-up 3.9 yrs) was tested with multivariable analyses, prognostic discrimination with ROC curves. Plasma levels of MR-proANP (206 [127–322] pM), CT-proET-1 (81 [64 –105] pM), MR-proADM (0.74 [0.58 – 0.97] nM) and CT-proAVP (13.8 [7.56 –24.2] pM) were elevated and correlated with traditional risk factors (age, NYHA class, ischemic etiology, diabetes, atrial fibrillation or COPD). All four biomarkers showed independent association with mortality (HR [95%CI] by medians): MR-proANP 2.52 [1.93–3.30], MR-proADM 1.81 [1.36 –2.40], CT-proET-1 1.79 [1.35–2.36], CT-proAVP 1.54 [1.21–1.98], all p<0.0001) and a prognostic discrimination (AUC range 0.70 – 0.74) similar to BNP (0.72), except for CT-proAVP (0.66). Novel and stable precursor fragments of vasoactive peptides are associated to known clinical risk factors and independently predict outcome in a large representative population of patients with chronic HF.