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MS; for the BEST InvestigatorsBackground-␤-Blockers improve survival and reduce hospitalization in chronic heart failure (CHF) by biologically improving left ventricular ejection fraction (LVEF). However, a good predictor of improvement with this therapy has not been identified. This substudy of BEST examined whether myocardial contractile reserve, as determined by dobutamine stress echocardiography, predicts improvement in LVEF. Methods and Results-Seventy-nine patients with class III/IV CHF underwent dobutamine stress echocardiography before treatment with bucindolol (nϭ41) or placebo (nϭ38). Regional wall motion score index (WMSI) was calculated as the sum of the scores in each segment divided by the total number of segments visualized. WMSI was compared with change in LVEF after 3 months of therapy as determined by gated radionuclide scan. Change in WMSI correlated inversely with change in LVEF after 3 months of bucindolol (rϭϪ0.72, PϽ0.0001) and was the most significant multivariate predictor of change in LVEF (Pϭ0.0002). Patients with contractile reserve had demographics similar to those of patients without contractile reserve, including RVEF, LVEF, systolic blood pressure, and CHF duration. However, patients without contractile reserve had higher baseline plasma norepinephrine levels (687Ϯ333 versus 420Ϯ246 pg/mL, PϽ0.05) and greater decrease in plasma norepinephrine in response to bucindolol (Ϫ249Ϯ171 versus Ϫ35Ϯ277 pg/mL, PϽ0.05). Conclusions-This study suggests a direct relationship between contractile reserve and improvement in LVEF with ␤-blocker therapy in patients with advanced CHF. Patients without contractile reserve have higher resting adrenergic drive, as reflected by plasma norepinephrine, and may experience greater sympatholytic effects from bucindolol.