Background: The response of sinoatrial node (SAN) to sympathetic stimulation is not completely revealed in patients with SAN dysfunctioin. Recent animal study suggests that the cranial shift of leading pacemaker site is impaired in canine model with pacing induced SAN dysfunction. This study was performed to demonstrate the impaired pacemaker hierarchy to sympathetic stimulation in patients with SAN dysfunction. Methods: SAN function and the leading pacemaker site was evaluated in 43 patients (31 males) with mean age of 55 짹 9 years using the 3D electroanatomic mapping system before and after isoproterenol infusion. The study group included 40 atrial fibrillations, 2 supraventricular tachycardia, and 1 pacemaker implantation patients. The patients were subgrouped according to without (Group 1; n = 33) and with (Group 2; n = 10) SAN dysfunction. Results: Baseline heart rate was lower in group 2 (54 짹 17 bpm) than group 1 (75 짹 12 bpm, p=0.001). SAN conduction time (346 짹 286, vs. 131 짹 48 ms, p=0.001) and corrected SAN recovery time (449 짹 324 ms, vs. 182 짹 86 ms, p=0.001) were significantly longer in group 2 than group 1. Atrial ERPs were not different between 2 groups. Three (9%) and 4 (40%) patients had right atrial scar in group 1 and 2, respectively (p=0.04). At baseline, the distribution of the leading pacemaker site was not different between two groups, with the superior SAN as the leading pacemaker site in 2 (6%) and 0 patients in group 1 and 2, respectively (p=1.00). However, during isoproterenol infusion, while the superior SAN served as the leading pacemaker site in 24 (73%) patient in group 1, only 3 (30%) patients in group 2 (P=0.02). The maximum heart rate during isoproterenol infusion was also significantly lower in group 2 (102 짹 28 bpm) than group 1 (124 짹 12 bpm, p=0.001). The increase of heart rate was significantly correlated with the cranial transition of the leading pacemaker site (R=0.83, p=0.001). Conclusion: In patients with SAN dysfunction, during sympathetic stimulation, the heart rate acceleration was significantly impaired, and the superior SAN did not serve as the leading pacemaker site. These findings suggest that the impaired function of superior SAN might be the one of the cause of chronotropic insufficiency in patients with SAN dysfunction.