Positron emission tomography (PET) imaging allows identification of stress-induced ischemia and myocardial viability in patients with ischemic cardiomyopathy. We assessed the left ventricular (LV) functional response to vasodilator stress in patients with advanced ischemic cardiomyopathy undergoing pharmacologic stress (PET) perfusion and metabolic imaging. Additionally, we aimed to determine if mitral regurgitation (MR), right ventricular (RV) dysfunction and diastolic function influenced the observed LV responses to pharmacologic stress. In 161 patients (81% men; 65 ± 13 years), PET and echocardiography were performed within a week for noninvasive evaluation of myocardial ischemia and viability (scored using 17-segment model), as well as ventricular and valvular function. Patients were stratified based on ischemic defects in any segments versus hibernation/scar defects only. The LV volumes, EF by gating and transient ischemic dilatation (TID) index were generated automatically. Wall thickening (WT) scores were determined visually. The subgroup with reversible/ischemic segments on PET imaging (N = 55) exhibited greater end-systolic (ESV) and end-diastolic volume (EDV) enlargement during stress (13 ± 22 and 16 ± 43 ml increase respectively, vs. 0 ± 18 ml [P < 0.0001] and 2 ± 24 ml [P = 0.01]), a decrease in LVEF during stress (mean −3% vs. +2%), and greater TID indices (mean 1.13 ± 0.18 vs. 1.02 ± 0.12) compared to hibernation/scar only (N = 92). In addition, mean WT scores during stress declined significantly only in the ischemic subgroup (P < 0.0001 for regional LAD, non-LAD and global wall thickening scores). The prevalence and the severity of MR and RV dysfunction did not differ between groups. By univariate analysis, global and LAD territory segmental ischemia, global sum stress score (SSS), TID index, resting EF, ESV enlargement during stress, as well as global WT changes correlated with post-stress LVEF decline. Multivariate predictors included SSS, resting LVEF, and ESV change. Ischemic changes on vasodilator PET imaging are associated with global LV functional decline and volumetric dilatation, presumably due to stunning effect. Severity of RV dysfunction and MR had limited impact on the above changes.