Clinical Significance of Endogenous Vasoactive Neurohormones in Chronic Systolic Heart Failure

Background: Neurohormonal 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 Results: In 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-I). 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 [nand regurgitation severity (P < .01 for all). Higher plasma levels of UCN-I 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-I >= 12 1 pM (HR 202. 95% CI 1.08-3 93, P = 029) and ET-1 >= 2.29 pM (HR 252, 95% CI 1 24-5.03. P = 011) remained significant independent risk factors for adverse clinical events Conclusion: Higher 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. (J Cardiac Fad 2010, 16 635-640)