This study was conducted with approval from the Ethics Committee of The Second Affiliated Hospital of Zhengzhou University (approval number 2018-019). As the nature of observational and retrospective study, informed consent was waived.
Selection of the study sample
This retrospective cohort study was conducted in the Cardiac surgery department of the Second Affiliated Hospital of Zhengzhou University from January 2017 to June 2020.
We target the recruitment of patients aged over 18, scheduled for isolated CABG, isolated valve, or combined CABG/valve surgery with cardiopulmonary bypass, who have a LVEF less than 40%, regardless of the method of assessment. All patients were consecutively evaluated. Exclusion criteria were: age < 18 years, preoperative renal failure (creatinine clearance < 30 ml/min), liver failure (prothrombine time < 50%, in the absence of vitamin K antagonist) Pregnancy, emergency surgery, defined as surgery within the 24 h of the operative indication.
During the study period, give the attending physician full discretion to administer any other medication, including levosimendan and other vasoactive drugs, as appropriate. Levosimendan was administered without a bolus, by continuous infusion at 0.2ug/kg/min for 24 h.
Data collection
Data were collected on: age; gender; body mass index > 24 kg/m2; hypertension; diabetes mellitus; cardiopulmonary bypass time; aortic cross-clamping and serum lactic acid levels.
Echocardiography was performed by the same team with three ultrasound operators at baseline, intraoperative and postoperative of each patient. The LVEF was measured using biplane Simpson’s method from the two-dimensional echocardiography.
All patients underwent continuous monitoring of heart rate and measurement of hemodynamic parameters including pulmonary artery occlusion pressure (PAOP) and cardiac index.
Time 0 was defined as the initial hemodynamic measurement, time 1 was recorded on arrival back in the cardiovascular ICU following surgery. Times 2 to 3 were 12 h and 24 h after arrival in the cardiovascular ICU following surgery, respectively.
Patients underwent 90 days of postsurgical follow-up, with survival status during this period being recorded.
Clinical definitions and study endpoints
LCOS incidence was the primary outcome of this trial. LCOS was defined as the presence of low cardiac index (< 2.2 L/min/m2)2, elevated PAOP (> 16 mmHg) and a SO2 < 60%. Secondary outcomes for this trial included (a) durations of ICU and hospital stay; (b) serum lactic acid levels at 0, 12, and 48 h post-surgery; (c) invasive hemodynamic parameters at 0, 12, and 48 h post-surgery.
Statistical analysis
Results were expressed as frequencies and percentages for categorical variables, and as means and standard deviations for continuous variables. Prior to propensity score matching, continuous variables were compared using Student’s t test or the Mann Whitney test, as appropriate. Qualitative variables were compared using Pearson s Chi-square or Fisher s exact test, as appropriate. Mortality at 90 days after cardiac surgery was estimated using the Kaplan Meier method and compared using the log-rank tests. A two-sided p < 0.05 was the significance threshold.
The propensity score was defined as the probability of exposure to levosimendan. In order to limit over adjustment due to the use of this score 5, we selected only the covariates most likely to introduce a confounding bias6. The propensity score was estimated using a logistic regression adjusted for age, sex, body mass index > 24 kg/m2, presence of high blood pressure and diabetes. Matching was then performed between one patient exposed to levosimendan and up to one unexposed patients7, with a propensity score caliper of 0.05.
After propensity score matching, Baseline demographic, clinical and echocardiographic data were estimated again to compare baseline characteristics and to therefore assess the accuracy of the matching procedure.
Associations between baseline factors and LCOS incidence were assessed using univariate analysis and multivariate logistic regression modeling. Hazard ratios (HR) and their 95% confidence intervals were calculated. A two-tailed p value < 0.05 was considered significant. All the statistical analyses were performed at the Second Affiliated Hospital of Zhengzhou University (Henan Province, China) with the use of SPSS software, version 25.0.