Adrenergic stimulation increases repolarization dispersion and reduces activation-repolarization coupling along the RV endocardium of patients with cardiomyopathy

Abstract

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 g/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 (R2 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. © 2009 Published on behalf of the European Society of Cardiology. All rights reserved.