Beta blockers improve left ventricular (LV) ejection fraction but patient responses are heterogenous. We investigated the role of contractile reserve (CR) in predicting beta-blocker response in ischemic and nonischemic cardiomyopathy. Resting and low-dose dobutamine echocardiograms were recorded in 32 patients with heart failure (LV ejection fraction <or=35%), 18 with ischemic cardiomyopathy (IC), and 14 with idiopathic dilated cardiomyopathy (IDC). A segment was defined as CR positive (CR+) or negative (CR-) based on response to dobutamine. Patients were then classified as CR+ or CR- based on number of improved segments (IC group) or ejection fraction improvement (IDC group) in response to dobutamine. During follow-up (2, 6, and 14 months after beta-blocker initiation), response was measured by the percent of segments showing improved contractility from baseline, ejection fraction, and wall motion score index. In the IC group, the percent of improved segments was greater at 2 and 6 months in CR+ versus CR- (70% vs 15% and 39% vs 17%, p <0.05), whereas it was greater at all periods in the patients with IDC (36% vs 9% at 2 months, 50% vs 19% at 6 months, and 63% vs 42% at 14 months, p <0.05). Findings for ejection fraction and wall motion score index were similar. Therefore, time course and magnitude of improvement in LV function in patients with heart failure receiving beta blockers are related to CR status. CR predicts a greater early response in IC, whereas it predicts a greater response at all time periods in IDC. However, even patients without CR showed improvement in LV function at 14 months.