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Objectives: Our study reports the first-in-human experience of a novel approach for left atrial access via the coronary sinus-the percutaneous atriotomy-which is used for left atrial decompression with a dedicated left atrial (LA)-to-coronary sinus (CS) shunt., Background: Elevated LA pressures contribute to heart failure symptoms, and targeted therapy with atrial shunt devices for LA decompression is an emerging strategy. Current devices reside in the interatrial septum, with risk for right-to-left shunting and systemic embolization. Moreover, preservation of the interatrial septum is imperative with an increasing number of left-sided transseptal transcatheter interventions., Methods: Patients with symptomatic heart failure underwent implantation in a multicenter, international compassionate experience. Clinical, anatomic, and hemodynamic parameters were assessed at baseline and follow-up. The right internal jugular vein enabled CS cannulation, followed by CS-to-LA puncture and balloon dilation of the LA wall, completing the percutaneous atriotomy. The novel shunt device was then deployed between the left atrium and CS, enabling LA decompression., Results: Percutaneous atriotomy was attempted in 11 patients, with success in 8; of these, all shunt deployments were successful. In follow-up (median 201 days; interquartile range [IQR]: 156 to 260 days) there were no major periprocedural adverse events, New York Heart Association functional class improved to I or II in 87.5%, pulmonary capillary wedge pressure was reduced (Δ -9 mm Hg; IQR: -9.5 to -8 mm Hg), and shunting was sustained (Δ Qp/Qs 0.25; IQR: 0.19 to 0.33)., Conclusions: Our study reports the first-in-human experience of a novel approach for left-sided transcatheter cardiac interventions: the percutaneous atriotomy. This approach enabled the placement of a novel LA-to-CS shunt for LA decompression. The procedure is feasible and results in clinical and hemodynamic improvements., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)