Study design and definitions

Following exemption from Nicklaus Children’s Hospital Research Institute institutional review board (exempt study# NCRI-EX-252), we retrospectively reviewed all available medical records, operative reports, cardiac catheterisation data, and echocardiographic data for all consecutive patients with functionally single ventricle who underwent first-time bidirectional cavopulmonary anastomosis operation from 1 January, 2006 to 31 December, 2019, at Nicklaus Children’s Hospital. Patients who underwent prior surgical interventions at an outside institution were excluded. Prematurity was defined as gestation age less than 37 weeks; low birth weight was defined as less than 2.5 kg, the genetic syndrome was defined as any anomaly identified by chromosomal karyotype or microarray, and weight-for-age Z-score at the time of bidirectional cavopulmonary anastomosis was calculated using the 2006 World Health Organization child growth standards. Interstage catheterizations were classified as elective and unplanned based on the documented indication in the catheterisation report. Catheterization data obtained from elective interstage catheterisation included systemic ventricle end-diastolic pressure, mean pulmonary artery pressure, pulmonary vein wedge pressure, and superior vena cava oxygen saturation. In the scenario where multiple samples were obtained for oxygen saturations, an average was used. If direct measurement of the mean pulmonary artery pressure was not obtained, the mean pulmonary vein wedge pressures were used as a surrogate, and if mean pressures between the left and right pulmonary artery were discrepant, an average of the two values was used. Although used in previous reports, pulmonary vascular resistance and cardiac index were excluded from our analysis due to multiple potential sources of errors related to assumed oxygen consumption and differences in pressures, flows, and sources of pulmonary blood flow. As graded by the expert imaging cardiologist who finalised the echocardiogram report, pre-operative assessments of atrioventricular valve function and ventricular function were determined based on the last complete echocardiogram performed prior to bidirectional cavopulmonary anastomosis. The severity of systemic atrioventricular valve regurgitation was dichotomised into two categories; 1) trivial to mild and 2) more than mild. Similarly, systemic ventricle function was dichotomised into two categories: 1) normal to mild dysfunction and 2) greater than mild dysfunction for the purpose of simple logistic regression. In order to assess the relationship between outcomes and increasing severity of systemic atrioventricular valve regurgitation and/or systemic ventricle dysfunction and accordingly generate effect plots, the pre-operative ventricular function was categorised into normal-fair function, mild, moderate, and severe dysfunction, and the systemic atrioventricular valve regurgitation was categorised into trivial, mild, moderate, and severe regurgitation.

The anatomical diagnosis was classified as:

1. 1. Classic hypoplastic left heart syndrome.

2. 2. Hypoplastic left heart syndrome variant: double-outlet right ventricle with mitral atresia and right ventricle dominant unbalanced complete atrioventricular canal defect.

3. 3. Single left ventricle with normally related great arteries: tricuspid atresia with normally related great arteries, severe Ebstein’s anomaly, pulmonary atresia with intact ventricular septum, and left ventricle dominant unbalanced complete atrioventricular canal defect.

4. 4. Single left ventricle with malposed/transposed great arteries: tricuspid atresia with transposed great arteries, double-inlet left ventricle with malposed great arteries, and double-outlet left ventricle with malposed great arteries.

5. 5. Heterotaxy.

6. 6. Biventricular CHD with good size ventricles which could not be septated.

We restricted our analysis to inpatient hospital outcomes; operative mortality was defined based on the Society of Thoracic Surgeons Congenital Heart Surgery Database criteria. Post-operative length of stay was measured from the day of surgery until discharge or death, and prolonged length of stay was defined as hospital stay greater than the 75^th percentile for our cohort.

Statistical analysis

All data processing and analyses were performed using the statistical programming language R. ²⁷ Data were described using means and standard deviations or medians and interquartile for continuous variables, counts, and percentages for categorical variables. To determine associations between pre-operative and intraoperative variables and the outcomes of interest, we performed simple logistic regression using tools from the R package DHARMa. ^{Reference Hartig28} Covariates with a p-value less than 0.1 on univariate analysis were included for multivariate logistic regression. The variance inflation factor of the fitted models was checked using the R package car, ^{Reference Fox29} and since variance inflation factor >5 indicates excessive collinearity, ^{Reference Yoo, Mayberry and Bae30} the variables with the highest variance inflation factor were successively removed until all variables were displayed variance inflation factor less than or equal to 5. The resulting model was checked for diagnostic issues using tools from the R package DHARMa. ^{Reference Hartig28} To evaluate the relationship between the increasing severity of pre-operative echocardiographic variables and outcomes of interest, estimated marginal means and contrasts were calculated using the R package Emmeans, ^{Reference Lenth, Singmann and Love31} and effects plots for composite failure and prolonged post-operative length of stay with pre-operative ventricular function and the systemic atrioventricular valve regurgitation were generated from logistic regression using the R package effects. ^{Reference Fox29}