Objective: We explored the incremental value of quantification of tissue Doppler (TD) velocity during the brief isovolumic contraction (IVC) phase of the cardiac cycle for the prediction of exercise performance in patients referred for cardiopulmonary exercise testing (CPET). Background: Experimental studies have shown that rapid left ventricular (LV) shape change during IVC is essential for optimal onset of LV ejection. However, the incremental value of measuring IVC velocities in clinical settings remains unclear. Methods: A total of 82 subjects (53짹14 years, 56 males) were studied with echocardiography and CPET. Reduced LV ejection fraction (EF < 50%) was present in 38 (46%) subjects. Pulsed-wave annular TD velocities were averaged from the LV lateral and septal annulus during isovolumic contraction (IVCa), ejection, isovolumic relaxation, early and late diastole (Aa) and compared with peak oxygen consumption (VO₂) and percentage of the predicted peak VO₂ (% predicted peak VO₂) obtained from CPET. Results: Patients with reduced EF had lower IVCa (6.3 vs. 4.5 cm/sec, P=0.04), ejection (7.7 vs. 5.5 cm/sec, P<0.001) and Aa velocities (7.9 vs. 6.6 cm/sec, P=0.04). Similarly, % predicted peak VO₂ was lower in patients with reduced EF (52.9 % vs. 73.1%, P < 0.001) and correlated with the variations in IVCa (r=0.7, p=0.001). Multivariate analysis of 2D and Doppler variables in presence of reduced LVEF revealed only IVCa and Aa as independent predictors of %predicted peak VO₂ (r²=0.612, P=0.02 for IVCa and P=0.009 for Aa). The overall performance of IVCa in the prediction of exercise capacity was good (area under curve= 0.86, P<0.001). Conclusion: Assessment of TD-derived IVC and atrial stretch velocities provide independent prediction of exercise capacity in patients with reduced LV ejection fraction. Assessment of LV pre-ejectional stretch and shortening mechanics at rest may be useful for determining the myocardial functional reserve of patients with reduced EF.