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Objectives: Postoperative atrial fibrillation (POAF) is a major complication after cardiac surgery, and an early postoperative introduction of beta-blockers is recommended to reduce its incidence. Landiolol, a new intravenous short-acting beta-1 blocker, could present a useful and safe macrohemodynamic profile after cardiac surgery. Detailed metabolic and hemodynamic effects of landiolol on cardiac performance, however, remain poorly documented. The authors aimed to investigate the dose-dependent hemodynamic and metabolic effects of landiolol in that specific setting., Design: A prospective, randomized, double-blind study versus placebo., Setting: A tertiary university hospital., Participants: Adult patients scheduled for elective cardiac surgery with cardiopulmonary bypass., Interventions: Incremental doses of intravenous landiolol (0.5, 1, 2, 5, and 10 μg/kg/min) were given within the 2 hours after arrival in the intensive care unit. Macrocirculatory parameters and cardiac performances were derived from transpulmonary thermodilution and transthoracic echocardiography. Metabolic data were obtained from arterial blood tests., Measurements and Main Results: From January to November 2019, 58 patients were analyzed and divided into a landiolol group (n = 30) and a control group (n = 28). Heart rate significantly decreased in the landiolol group (p < 0.01), whereas mean arterial pressure and stroke volume remained unchanged. No significant modification was found in both left and right systolic and diastolic performances. Metabolic variables were similar in both groups. New-onset POAF occurred in 9 (32%) versus 5 (17%) patients in the control and landiolol groups, respectively (p = 0.28)., Conclusions: Infusion of landiolol in the range of 0.5-to-10 μg/kg/min during the early postoperative period presents a good macrohemodynamic safety profile in cardiac surgical patients and could be useful to prevent POAF., Competing Interests: Declaration of Competing Interest Arnaud Ferraris: Invited in conferences for Amomed Pharma. Jean-Luc Fellahi: Invited in conferences and advisory board Amomed Pharma., (Copyright © 2022 Elsevier Inc. All rights reserved.)