Levosimendan administration and survival in patients receiving mechanical circulatory support: insights from an unselected real-world cohort

Background Mechanical circulatory support (MCS) strategies such as Impella CP, veno-arterial extracorporeal membrane oxygenation (VA-ECMO), and combined ECMELLA provide temporary hemodynamic stabilization in refractory cardiogenic shock. Despite advanced support, mortality remains high and vasoactive therapy is frequently required. While norepinephrine, epinephrine, and dobutamine represent standard treatment, the prognostic relevance of levosimendan administration in this setting remains uncertain. Purpose To evaluate the association between levosimendan administration and short- and long-term survival in patients treated with MCS, including those undergoing prior cardiopulmonary resuscitation (CPR). Methods We retrospectively analyzed 307 consecutive patients treated with MCS at our facility between 2014 and 2024. Baseline characteristics, comorbidities, laboratory values, vasoactive medication exposure, resuscitation status, and device strategy were collected. The primary endpoint was 30-day mortality. Secondary endpoints included survival to hospital discharge and long-term survival. Vital status was obtained through official registry data. Multivariable logistic regression adjusted for age, sex, device strategy, lactate at admission, resuscitation status, and peak norepinephrine dose within the first 24 hours. Long-term survival was analyzed using Kaplan–Meier estimates. Results Among 307 patients, 84 (27%) received levosimendan within 24 hours of MCS initiation. Thirty-day mortality was lower in patients receiving levosimendan compared with those who did not (67.9% vs. 83.9%). After multivariable adjustment, early levosimendan use remained independently associated with reduced 30-day mortality (adjusted OR 0.46, 95% CI 0.22–0.98; p = 0.045). Higher peak norepinephrine dose (adjusted OR 1.78 per mg/h; p < 0.001), elevated lactate, and increasing age were independently associated with mortality. In patients undergoing CPR prior to MCS initiation, levosimendan was strongly associated with improved survival (adjusted OR 0.25, 95% CI 0.09–0.65; p = 0.006). Kaplan–Meier analysis demonstrated sustained survival differences during long-term follow-up. Conclusion In this retrospective real-world MCS cohort, levosimendan administration was independently associated with reduced short-term mortality and improved long-term survival, including in resuscitated patients. While residual confounding inherent to the observational design cannot be excluded, these findings support prospective evaluation of levosimendan as adjunctive therapy in advanced cardiogenic shock.