Clinical Significance of Endogenous Vasoactive Neurohormones in Chronic Systolic Heart Failure

BackgroundNeurohormonal activation is a pathophysiological hallmark of acute and chronic heart failure (HF). The clinical significance of more recently discovered endogenous vasoactive hormones has not been well-characterized.Methods and ResultsIn 154 subjects with stable, chronic systolic HF (New York Heart Association Class I-IV, left ventricular LV] ejection fraction ≤40%), we measured plasma levels of urocortin 1 (UCN-1), urotensin II (UT-II), and endothelin-1 (ET-1) and performed comprehensive echocardiography with assessment of cardiac structure and performance. Adverse clinical events (all-cause mortality, cardiac transplantation or HF hospitalization) were prospectively tracked for a median of 39 months. Plasma levels of UCN-1 and ET-1 (but not UT-II) increased with LV diastolic dysfunction stage, right ventricular systolic dysfunction class, and mitral regurgitation severity (P < .01 for all). Higher plasma levels of UCN-1 and ET-1 (but not UT-II) predicted increased risk for adverse clinical events. After adjustment for age, LV ejection fraction, and plasma amino-terminal pro-B-type natriuretic peptide, plasma UCN-1 ≥12.1 pM (HR: 2.02, 95% CI: 1.08-3.93, P = .029) and ET-1 ≥2.29 pM (HR: 2.52, 95% CI: 1.24-5.03, P = .011) remained significant independent risk factors for adverse clinical events.ConclusionHigher levels of plasma levels of UCN-1 and ET-1 but not UT-II were associated with worse LV diastolic performance and poorer long-term clinical outcomes in patients with chronic systolic HF.