Discussion
primary graft dysfunction, postcardiotomy cardiogenic shock
PRIMARY GRAFT DYSFUNCTION
Our study did not find any association of levosimendan administration and ECMO weaning success or mortality in patients with refractory postcardiotomy cardiogenic shock. To our knowledge, this is the first emulated target trial evaluating the potential effect of levosimendan on ECMO weaning and mortality in this population.These results are consistent with the latest observational studies [Our study shows a number of strengths. The methodological framework known as "emulated target trial" [To date, all studies regarding the effect of levosimendan on ECMO weaning have been retrospective cohort studies and therefore all treatment effect estimates are at risk of confounding. Few studies [Our study also has some limitations. First, even if we used the target trial framework, the study gets some limitations due to its observational nature: data were collected retrospectively, available information restrain the possibilities to define eligibility criteria, and blinding could not be emulated (even if in the setting of this particular study, we would have expected a minimal risk of performance and information biases). Second, missingness was present. Nonetheless, the proportion of missing data was low, and we imputed these data with multiple imputation, in a way that takes advantage of longitudinal collection of the data [Fifth, the dosage of levosimendan administered in our study (0.2 µg/kg/min) is in accordance with the label dosage (maximum dosage). To our knowledge, the only pharmacological study of levosimendan under ECMO by Sangalli et al. [Sixth, the main cause of refractory postcardiotomy cardiogenic shock in our study was acute primary graft dysfunction. Therefore, the results of our study should be cautiously applied to other tertiary centers with more prevalent subpopulations at higher risk of failure of ECMO weaning (valvular, aortic and combined surgery) than patients after heart transplantation [Finally, we could not control timing of administration of levosimendan as in a randomized trial, and the time between ECMO implantation and levosimendan administration was a median of 5 days [The positive inotropic effect of levosimendan is prolonged because of 80-h half-life of the active metabolite OR-1896 [