AIMS Dispersion of repolarization (DOR) in the human heart is minimized by activation-repolarization coupling. Adrenergic stimulation can be proarrhythmic in patients with impaired left-ventricular function and its effect on repolarization dispersion has not been systematically investigated. Our objective was to study the effect of dobutamine on repolarization dispersion and activation-repolarization coupling in patients with cardiomyopathy. METHODS AND RESULTS Activation recovery intervals (ARI) and activation times (AT) were measured from unipolar electrograms at 10 sites along the apicobasal right ventricle (RV) in 14 patients with cardiomyopathy (LVEF < 40%). These measurements were made during control, dobutamine 2.5-5.0 microg/kg/min, and a recontrol phase while maintaining constant heart rates with atrial pacing. Dispersion of repolarization was calculated from the total recovery time (TRT, AT+ARI). Activation-repolarization coupling was assessed by linear regression of ARI and AT. Dispersion of repolarization across all 10 sites and between adjacent sites increased with dobutamine compared with control (whole DOR: range 15 +/- 2 vs. 12 +/- 2 ms, P = 0.06 and standard deviation 5.5 +/- 0.9 vs. 4.3 +/- 0.9 ms, P = 0.04; adjacent DOR: 5.9 +/- 0.8 vs. 4.5 +/- 0.6 ms, P = 0.04). This was associated with shallower ARI/AT slopes (-0.3 +/- 0.2 vs. -0.8 +/- 0.2, P = 0.05) and a decrease in ARI-AT correlation (R(2) 0.4 +/- 0.1 vs. 0.6 +/- 0.1, P = 0.05) with dobutamine compared with control. CONCLUSION Adrenergic stimulation increases apicobasal RV DOR and reduces coupling between activation and repolarization in patients with cardiomyopathy. This may provide a mechanism for the proarrhythmic potential of heightened adrenergic states in these patients.