The purpose of this study was to examine the relationship between noninvasive measurements of ventricular-vascular coupling (VVC) with exercise tolerance, and compared the value of VVC versus other traditional determinants of exercise capacity in this population. 43 patients with ischemic CMP (age 59 +/- 9 years, mean EF 24 +/- 8%) underwent cardiopulmonary exercise testing, echocardiography and cardiac magnetic resonance (CMR). VVC was defined non-invasively by the ratio of ventricular systolic elastance (Ees) to the arterial elastance (Ea), where Ees = end-systolic pressure/end-systolic volume index and Ea = end-systolic pressure/stroke volume index. VVC significantly correlated with baseline heart rate (HR), peak exercise systolic blood pressure, maximum oxygen consumption (MVO(2)) and peak O(2) pulse (MVO(2)/HR). A higher VVC was associated with higher LVEF and RVEF but showed inverse relation to mitral E wave velocity. Univariate predictors of MVO(2) are baseline HR, chronotropic reserve, VVC and aortic distensibility; whilst mitral E wave velocity, LVEF, VVC, Ees significantly correlated with peak O(2) pulse. By stepwise multivariate analysis, VVC remained the only independent predictor of peak O(2) pulse. Ventricular-vascular coupling at rest may be a clinically important parameter in predicting exercise capacity in patients with advanced heart failure, and may become an additional target for therapeutic interventions.