Harlequin Syndrome in Venoarterial ECMO and ECPELLA: When ECMO and Native or Impella Circulations Collide - A Comprehensive Review.

Harlequin syndrome, also known as differential hypoxia (DH) or North-South syndrome, is a serious complication of femoro-femoral venoarterial extracorporeal membrane oxygenation (V-A ECMO). Moreover, Harlequin syndrome is caused by competing flows between the retrograde oxygenated ECMO output and the anterograde ejection of poorly oxygenated blood from the native heart. In the setting of impaired pulmonary gas exchange, the addition of an Impella device (ECPELLA configuration), although beneficial for ventricular unloading and hemodynamic support, may further exacerbate this competition and precipitate DH. This narrative review synthesizes current evidence on the pathophysiology, diagnostic strategies, and management of DH in patients supported with V-A ECMO or with ECPELLA. Meanwhile, the timely detection of Harlequin syndrome is essential to prevent cerebral and myocardial hypoxia. Current diagnostic approaches include right radial arterial pressure monitoring, multisite arterial blood gas analysis, cerebral oximetry, and echocardiographic evaluation of flow dynamics. Interestingly, emerging tools such as contrast-enhanced ultrasound (CEUS) and suprasternal transthoracic echocardiography (TTE) show promise for non-invasive bedside identification of flow competition. However, further management of DH requires tailored strategies aimed at restoring adequate oxygen delivery while preserving sufficient ventricular ejection or Impella support. Moreover, circuit reconfiguration remains a key rescue option when conventional optimization fails. This review highlights that successful treatment depends on integrating real-time physiological data with a dynamic understanding of circulatory support, emphasizing the need for multidisciplinary expertise in managing this complex syndrome.