Effect of Levosimendan on Ventricular Systolic and Diastolic Functions in Heart Failure Patients: A Meta-analysis of Randomized Controlled Trials

ABSTRACT Levosimendan, a calcium sensitizer, exerts inotropic action through improving left ventricular ejection fraction. We noticed that only few clinical studies are published in which the effects of levosimendan on cardiac function are studied by echocardiography. When screening the literature (PubMed, Embase and CENTRAL, from inception to August 2020), we found 29 randomized controlled trials on levosimendan containing echocardiographic data. We included those studies, describing a total of 574 heart failure patients, in our meta-analysis and extracted 14 ultrasonic parameters, pooling the effect estimates using a random-effect model. Our analysis of the diastolic parameters of the left ventricle shows that levosimendan reduce the early/late trans-mitral diastolic peak flow velocity (E/A) ratio (SMD -0.45, 95%CI (-0.87, -0.03), P=0.037) and E/e' (e': mitral annulus peak early diastolic wave velocity using tissue-doppler imaging) (SMD -0.59, 95%CI (-0.8, -0.39), P<0.001). As it regards the systolic parameters of the right ventricle, levosimendan increased tricuspid annular plane systolic excursion (SMD 0.62, 95%CI (0.28, 0.95), P<0.001) and tricuspid annular peak systolic velocity (SMD 0.75, 95%CI (0.35, 1.16), P<0.001), and reduced systolic pulmonary artery pressure (SMD -1.02, 95%CI (-1.32, -0.73), P<0.001). As it regards the diastolic parameters of the right ventricle, levosimendan was associated with the decrease of Aa (peak late diastolic tricuspid annular velocity using tissue-doppler imaging) (SMD -0.38, 95%CI (-0.76), 0, P=0.047) and increase of Ea (peak early diastolic tricuspid annular velocity using tissue-doppler imaging) (SMD 1.03, 95%CI (0.63, 1.42), P<0.001) and Ea/Aa (SMD 0.86, 95%CI (0.18, 1.54), P=0.013). We show that levosimendan is associated with an amelioration in the diastolic and systolic functions of both ventricles in HF patients.