The mechanisms of the N-terminal-pro-brain natriuretic peptide (NT-pro-BNP) release in intensive care unit (ICU) patients with preserved ejection fraction (EF) are unclear. We investigated whether left ventricular (LV) dysfunction, as assessed by tissue Doppler imaging (TDI), is related to NT-pro-BNP levels in ICU patients with preserved EF and has a complementary value to NT-pro-BNP in the determination of in-hospital mortality. We examined 58 mechanically ventilated patients with no history of heart failure (age, 60 +/- 18 years; EF, 63% +/- 7%). The systolic (S) and early diastolic (E') velocity of the mitral annulus by TDI and the E/E' as well as NT-pro-BNP, troponin, lactate acid, blood oxygen (P(O2)/Fi(O2)), sepsis, and ICU mortality were assessed. Systolic, E', and E/E' correlated with age, P(O2)/Fi(O2), lactate acid, NT-pro-BNP, troponin, history of arterial hypertension, and diabetes (P < 0.05). By multivariate analysis, the determinants of NT-pro-BNP were S (P = 0.024), E/E' (P = 0.017), and sepsis (P = 0.015). An NT-pro-BNP greater than 941 pg/mL was a reliable predictor of LV diastolic dysfunction defined as a composite of E' less than or equal to 8 cm/s and/or mean E/E greater than or equal to 13 (area under the curve, 75%; P = 0.03). Patients with combined NT-pro-BNP greater than 941 pg/mL and abnormal TDI markers had increased creatinine levels and a lower MAP, P(O2)/Fi(O2), and survival rate than those with abnormal TDI or NT-pro-BNP alone or patients with normal TDI markers and NT-pro-BNP (25%, 60%, 70%, and 84%, respectively; P < 0.05). The addition of abnormal TDI in a model including NT-pro-BNP and sepsis increased the model's value for in-hospital mortality (P for change = 0.01). In ICU patients with preserved EF, LV diastolic dysfunction and sepsis determine NT-pro-BNP levels. Tissue Doppler imaging markers and NT-pro-BNP have a complementary value for in-hospital mortality.