Left ventricular (LV) systolic and diastolic parameters derived from Doppler echocardiography have been used widely to predict functional capacity but diastolic filling is affected by various factors. Tissue Doppler imaging (TDI) that records systolic and diastolic velocities within the myocardium and at the corners of the mitral annulus, has been shown to provide additional information about regional and global LV function. The goal of this study was to examine whether TDI-derived parameters add incremental value to other standard Doppler echocardiographic measurements in predicting exercise capacity. The study enrolled 59 consecutive patients with stable congestive heart failure (CHF). The etiology of heart failure was coronary artery disease in 42 patients and dilated cardiomyopathy in 17. Twenty-three age-matched healthy subjects were recruited as controls. Conventional echocardiographs and TDI were obtained. Early (Ea) and late (Aa) diastolic and systolic (Sa) mitral annulus velocities, the Ea/Aa and E/Ea ratios, were measured by pulsed wave TDI placed at the septal side of the mitral annulus and results were compared with results of cardiopulmonary exercise testing. Systolic and early diastolic velocities of mitral annulus were decreased and the E/Ea ratio was increased in the restrictive group as compared to controls (P = 0.02, P = 0.03, P < 0.001, respectively) but there was no significant difference in late diastolic velocity and the Ea/Aa ratio between the restrictive group and controls. The average peak VO2 of the patients were 14.9 +/- 4.9 ml/min per kg. Achieved peak VO2 of the patients with E/Ea ratio <or=7.5 was 17.4 +/- 5 vs 12.2 +/- 3 ml/min per kg for those with E/Ea >7.5 (P < 0.001). Interestingly, the patients with the nonrestrictive pattern and E/Ea ratio >7.5 had reduced exercise capacity, as did the group with restrictive LV filling patterns (12.8 +/- 3.3 vs 12.9 +/- 4.0 ml/min per kg, P = 0.9). Similarly, there was no significant difference in the mean exercise capacity between the patients with a nonrestrictive pattern vs restrictive pattern with E/Ea ratio <or=7.5 (16.1 +/- 5.0 vs 15.4 +/- 5.1 ml/min per kg, P = 0.78). Univariate analysis demonstrated that the peak Sa (r = 0.30, P = 0.03), peak Ea (r = 0.38, P = 0.004) and peak Aa (r = 0.35, P = 0.009) correlated significantly with maximum exercise capacity. No relationship was observed between the Ea/Aa ratio and peak VO2 (r = -0.09, P = 0.48). By multivariate analysis, including age and heart rate, the E/Ea ratio was found to be an independent prognostic factor at peak VO2 (P < 0.001. In contrast, the comparison of the maximum transmitral early diastolic velocity and the mitral annulus TDI velocity, that is E/Ea ratio, had strong correlation with peak VO2 (r = -0.46, P < 0.001). Receiver operating characteristic (ROC) analysis was performed for prediction of limited exercise capacity from the E/Ea ratio. An E/Ea ratio <or=7.5 was able to predict peak VO2 <or=14 ml/min per kg with a sensitivity of 84% and a specificity of 74%. If restrictive pattern or an E/Ea ratio >7.5 was used, 21 out of 24 patients in the reduced exercise capacity group were identified with 16 false positives in the preserved exercise capacity group (P = 0.001). Mitral annular systolic and diastolic velocities of TDI were associated with cardiopulmonary exercise capacity in patients with LV systolic dysfunction. Index of the E/Ea ratio was found to be the most powerful predictor of peak oxygen uptake.