BACKGROUND In severe aortic stenosis (AS), brain natriuretic peptide (BNP) and its precursor, the amino-terminal pro-hormone (NT-proBNP) are independent predictors of outcome. Deterioration of cardiac function in AS is currently assessed by symptomatology and echocardiography to determine the optimal time point for surgery. We investigated whether BNP or NT-proBNP may help to estimate the individual risk of patients for subendocardial ischaemia in patients with moderate and severe AS. METHODS In 71 patients with AS and 24 controls, the association of plasma natriuretic peptides with invasively measured haemodynamic parameters, including the myocardial oxygen supply-to-demand ratio [diastolic pressure time index/systolic pressure time index (DPTI/SPTI)] was cross-sectionally assessed. RESULTS Levels of natriuretic peptides increased with severity of AS. In patients with moderate AS (n = 30), natriuretic peptides differentiated between symptomatic and asymptomatic status (P = 0.01). BNP and NT-proBNP values correlated negatively with DPTI/SPTI (r = -0.58 and -0.51, P < 0.001, respectively) and left ventricular (LV) ejection fraction (EF) (r = -0.52 and -0.59, P < 0.001, respectively). DPTI/SPTI correlated with aortic valve area (P < 0.0001) but not with EF. Receiver operating characteristic analysis determined cut-off values of > 450 pg mL(-1) for BNP and of > 1800 pg mL(-1) for NT-proBNP for those AS patients who were at highest risk for subendocardial ischaemia (i.e. DPTI/SPTI < 0.22) in combination with impaired LV systolic function (i.e. EF < 45%). CONCLUSIONS Elevated natriuretic peptides show cardiac deterioration in AS and may help to identify those patients in need for early valve replacement.