Apelin is a newly discovered inotropic peptide tentatively linked up with the pathophysiology of heart failure (HF). To further assess the role of apelin in HF, we measured its transcardiac arteriovenous gradients in patients with left ventricular pressure overload with or without HF and in patients with structurally normal hearts. Blood samples from the aortic root and coronary sinus were drawn from 49 adult patients undergoing preoperative cardiac catheterization for severe aortic valve stenosis (AS). Similar samples were taken from 12 control patients with structurally normal hearts undergoing electrophysiological studies. Plasma apelin was determined by enzyme immunoassay. In the control group, apelin decreased from a median of 0.39 (0.16-1.94) ng/ml in the aortic root to 0.18 (0.13-1.04) ng/ml in the coronary sinus (P = 0.004). In AS patients free of HF (n = 33), apelin concentration remained unaltered across the heart, but in those with HF (n = 15) apelin rose from a median of 0.26 (0.20-0.82) ng/ml in the aorta to 0.45 (0.24-1.17) ng/ml in the coronary sinus (P = 0.002). The transcardiac apelin gradients differed statistically highly significantly across the three groups (P = 0.00005), and each of the two-group differences was also statistically significant (P < 0.05). In conclusion, left ventricular pressure overload changes the transcardiac arteriovenous differences of circulating apelin. Although normal hearts extract apelin from the coronary blood, hearts failing due to left ventricular pressure overload release apelin into the circulation. Loss of cardiac apelin may be involved in the mechanisms of HF development in AS.