The Use of Levosimendan in Patients Undergoing Left Ventricular Assist Device Implantation to Mitigate the Risk of Early Postoperative Right Heart Failure (Euro LEVO-LVAD Study): An Analysis of the EUROMACS Registry

Abstract

Purpose Right heart failure (RHF) has been reported in 20% to 50% of patients receiving an LVAD. However, optimal management strategies are not well described. In the EUROMACS RHF score study, early severe RHF was reported in 22% of patients on LVAD. Patients who developed RHF had significantly increased mortality. Furthermore, patients who develop severe RHF have a 4-fold increase in the length of ICU stay. In contrast to conventional inotropes, levosimendan (LEVO) is a first-in-class inotropic agent that acts as a calcium sensitizer. It increases cardiac output and stroke volume and reduces peripheral vascular resistance without increasing myocardial oxygen consumption, and therefore without an increased risk of serious arrhythmia or myocardial “exhaustion”. Furthermore, it has a long therapeutic effect that may last for weeks, due to the long half-life of one of its active metabolites. In a recent two meta-analyses, LEVO use was associated with improvement of a wide range hemodynamic and clinical outcomes in patients undergoing ECMO support or in patients with ambulatory end-stage heart failure. The aim of our study was to evaluate the effect of levosimendan on early postoperative RHF, major adverse effects, and mortality in patients undergoing LVAD implantation Methods The EUROMACS registry was used to identify adult patients with contemporary continuous-flow LVAD implantations. The index cohort (n=393) comprises patients on LVAD who received perioperative LEVO. The control cohort will be identified from the registry (n=3856) via propensity score matching. Matched patients with and without perioperative use of LEVO will be compared for baseline, procedural characteristics as well as co-medication. Differences between groups will be assessed by the student's t-test, Chi-squared test, and Kruskal-Wallis tests when appropriate. Kaplan-Meier curves will be reconstructed for 30-day and 1-year survival between the two cohorts Endpoints The primary endpoint is the rate of early (30 days) postoperative RHF between LEVO and no LEVO cohort. Secondary endpoints are 30-day and 1-year survival. Other secondary endpoints include ICU and hospital length of stay, major or life-threatening bleeding, stroke, AKI, thromboembolism, sepsis, and multiorgan failure Right heart failure (RHF) has been reported in 20% to 50% of patients receiving an LVAD. However, optimal management strategies are not well described. In the EUROMACS RHF score study, early severe RHF was reported in 22% of patients on LVAD. Patients who developed RHF had significantly increased mortality. Furthermore, patients who develop severe RHF have a 4-fold increase in the length of ICU stay. In contrast to conventional inotropes, levosimendan (LEVO) is a first-in-class inotropic agent that acts as a calcium sensitizer. It increases cardiac output and stroke volume and reduces peripheral vascular resistance without increasing myocardial oxygen consumption, and therefore without an increased risk of serious arrhythmia or myocardial “exhaustion”. Furthermore, it has a long therapeutic effect that may last for weeks, due to the long half-life of one of its active metabolites. In a recent two meta-analyses, LEVO use was associated with improvement of a wide range hemodynamic and clinical outcomes in patients undergoing ECMO support or in patients with ambulatory end-stage heart failure. The aim of our study was to evaluate the effect of levosimendan on early postoperative RHF, major adverse effects, and mortality in patients undergoing LVAD implantation The EUROMACS registry was used to identify adult patients with contemporary continuous-flow LVAD implantations. The index cohort (n=393) comprises patients on LVAD who received perioperative LEVO. The control cohort will be identified from the registry (n=3856) via propensity score matching. Matched patients with and without perioperative use of LEVO will be compared for baseline, procedural characteristics as well as co-medication. Differences between groups will be assessed by the student's t-test, Chi-squared test, and Kruskal-Wallis tests when appropriate. Kaplan-Meier curves will be reconstructed for 30-day and 1-year survival between the two cohorts The primary endpoint is the rate of early (30 days) postoperative RHF between LEVO and no LEVO cohort. Secondary endpoints are 30-day and 1-year survival. Other secondary endpoints include ICU and hospital length of stay, major or life-threatening bleeding, stroke, AKI, thromboembolism, sepsis, and multiorgan failure