Table 2.

Summary of previous published papers describing the effect of levosimendan on pediatric heart failure population.

Author, year and study design	Study population	Sample size	Intervention and control group	Main results
Namachivayam, 2006 (29) Case series	End stage or acute HF	15 patients	Single or repeated doses of levosimendan No control group.	Reduction on the dosage of dobutamine at day 5. Improvement of LV EF in the acute HF group. 1 patient had ventricular tachycardia. 4 patients died during the ICU hospitalization.
Ryerson, 2011 (30) Case Series	Severe decompensated HF, chronically dependent of IV vasoactive drugs	9 patients	Levosimendan rotation with dobutamine and/or milrinone No control group.	Helped to the discharge of ICU and wean of invasive mechanical ventilation. 2 deaths in hospital No improvement on LV ejection fraction
Prijić, 2011 (31) Case series	Severe decompensated HF with congenital or acquired heart disease chronically dependent of IV vasoactive drugs	3 patients	Levosimendan initiation and stop the previous vasoactive regimen No control group.	Clinical and echocardiography improvement with the improved EF and stroke volume. Reduction in heart rate in all the treated patients Normalization of lactate
Bravo, 2011 (32) Prospective, case series	Infants with CHD with low cardiac output syndrome refractory to conventional treatment	5 patients (7 doses of levosimendan)	Levosimendan (2 patients with repeated dosages)	Reduction on lactate and heart rate Improved the cerebral intravascular oxygenation (NIR-SRS parameters)
Suominen, 2011 (33) Single center, Retrospective descriptive data and survey data	3 groups: Cardiac surgery group (pre- peri or postoperative) Cardiac failure group (ADHF) Dilated cardiomyopathy group (acute or chronic HF)	293 patients (484 infusions)	Levosimendan (single or repeated infusions) No control group.	Descriptive data on use of levosimendan regarding gender distribution, median age, duration of infusion and interval between repeated dosages. For the efficacy and adverse events analysis, the results were based on the survey information. For 88.9% of the respondents levosimendan was considered as safe and efficacious The physicians were able to recall as adverse events: hypotension (62.1%), tachycardia (27.8%) occurred in the beginning of the infusion or no adverse events (27.8%).
Apostolopoulou, 2018 (34) Retrospective, single center.	End-stage pediatric HF or CHD refractory to treatment, functional class III or IV, chronically dependent of IV vasoactive and inotropic support.	27 patients	Long-term continuous intravenous ambulatory inotropic support (milrinone and dobutamine) and/or periodic levosimendan infusions as bridging to recovery, bridge to therapy or destination No control group.	Ambulatory inotropy – median time duration 1.0 (0.3–3.7) years Bridge to recovery: 6 patients with myocarditis, 4 with ambulatory inotropic + levosimendan and 2 with repeated infusions of levosimendan. All recovered. Bridge to heart transplant: 6 patients, 4 received ambulatory inotropic + levosimendan and 2 with repeated infusions of levosimendan. 3 deaths. Mainstain therapy: 15 patients, 1 received a VAD, 6 received ambulatory inotropic + levosimendan and 4 with repeated infusions of levosimendan. 4 deaths, median follow-up 2.1 (0.3–21.3) years. Adverse events: 4 central line infection or 4 central line dislodgements.