The aim of this study was to investigate the relative contributions of left ventricular hypertrophy (LVH) and myocardial ischemia to the association between abnormal myocardial deformation during dobutamine stress echocardiography (DSE) and mortality.Both left ventricular hypertrophy (LVH) and myocardial ischemia are known to convey a significant adverse prognostic impact. In addition, myocardial deformation is an independent predictor of outcome in patients undergoing DSE. The mechanism of this association, however, is undefined.We studied 223 consecutive individuals with normal resting LV function undergoing DSE. The LV mass was indexed to height (g/m(2.7)) (LVMI), and LVH was designated as LVMI >or=51 g/m(2.7). Myocardial ischemia was defined on the basis of new, inducible wall motion abnormalities. Customized software was used to measure global strain rate (SRs), which was averaged in 18 myocardial segments at peak stress. Individuals were followed for all-cause mortality over a mean of 5.4 +/- 1.4 years.Left ventricular hypertrophy was identified in 83 individuals (37%), and 63 (28%) had ischemia documented at DSE. In a Cox proportional hazards model, the strongest predictor of all-cause mortality for the total population was SRs (hazard ratio: 2.16, 95% confidence interval: 1.63 to 2.87, p < 0.01). Both LVH (p < 0.01) and ischemia (p < 0.05) had a significant adverse prognostic impact. Individuals with both LVH and ischemia had the worst outcome (p = 0.02) in comparison with the rest of the population. Among LV geometric patterns, concentric LVH had the worst outcome (p < 0.01). However, SRs was the strongest predictor of mortality in both LVH and ischemia. In a model reflecting clinical practice, SRs provided a significant increment in model power over baseline and variables identified at DSE.The SRs is a powerful, independent predictor of all-cause mortality in individuals undergoing DSE and provides incremental information over baseline clinical and echocardiographic variables. Whereas SRs is influenced by both LVH and myocardial ischemia, both independently and additively, its predictive power for mortality is independent of both.