Study design and participants
This observational cohort study was conducted at Fuwai Hospital and included children under 18 years old at the time of HTx from October 1, 2005, to May 31, 2023. In order to compare the overall prognosis of HTx in children and adults, we also collected basic information on adult patients who underwent HTx at our center during the same period. The study excluded cases of combined transplantation, such as heart and kidney or heart and liver transplantation. We excluded patients with a history of re-transplantation [8].The immunosuppression protocol was modified from the standard Stanford protocol to include prophylaxis for pneumocystis carinii with sulfamethoxazole and terminal methicillin. Additionally, oral antifungal prophylaxis with amphotericin was administered for 3–6 months. Orphans from institutionalized or single-parent families were excluded from the study, as the composite measure of socio-economic status requires information from both parents. Moreover, families facing financial difficulties were encouraged to apply for charitable funds to cover the cost of surgery and related expenses. Patients who were discharged alive after surgery were included in the follow-up cohort. The study protocol and publication of data were approved by the Institutional Review Board under ethical approval number 2022 − 1727, and informed consent was obtained from all the participants and each child’s parent or guardian.
Procedures
Baseline clinical and demographic data of all enrolled patients were collected from electronic medical records (EMR), outpatient consultations, and telephonic follow-up communications. Clinical information included previous surgical history, weight, etiological diagnosis of HTx, date of operation, intensive care unit (ICU) days, hospital days, and total postoperative hospital costs. Demographic information encompassed age at surgery, gender, residence in urban or rural areas, and residence in poverty-stricken areas. Urban and rural areas were categorized according to the Provisions on the Statistical Division of Urban and Rural Areas issued by the National Bureau of Statistics in 2008. Poverty-stricken areas were determined based on the list of 832 poor counties issued by the National Rural Revitalization Administration in 2014.
Patients discharged alive underwent outpatient appointments at our center at 1-, 6-, and 12-month intervals post-discharge, followed by annual visits. These appointments involved routine examinations to evaluate cardiac function and collect information regarding general health status and any readmission events. Efforts were made to contact patients who missed their scheduled follow-up visits by reaching out to their parents or guardians via telephone. Questionnaires were administered to gather data on survival status, general health, attendance at cardiac clinic follow-ups, and details of any readmissions, including dates and reasons(Details can be seen the supplementary file). Patients who could not be contacted were classified as lost to follow-up. The median follow-up period was 60 months, ending on September 30, 2023. Patients lost to follow-up were considered alive as of their last known contact date.
Past research has found that children’s health status and access to care are associated with parental socio-economic level, which also influences the risk of cardiovascular diseases [4, 9]. Using a questionnaire to know the socio-economic level of the child’s family has been successfully used in previous study from our center [10]. We referenced previous research methods to create a composite family socio-economic status score that included family income in the past year, as well as the occupation and education level of each parent in the family [9].All questionnaires were administered at the same time as the day of discharge from hospital after HTx, and informed consent was obtained from the patient’s family for the completion of these questionnaires. Parental occupation was divided into manual worker, farmer, or unemployed (low, score 1); businessman or clerk (medium, score 2); and professional, manager, or government employee (high, score 3). Annual household income was categorized as low (<¥10 000, score 1), medium-low (¥10 000–29 999, score 2), medium (¥30000–49999, score 3), medium-high (¥50 000–99 999, score 4), and high (≥¥100 000, score 5). Parental education level was categorized as less than high school (low, score 1), high school graduate or equivalent (medium, score 2), and college graduate or above (high, score 3). The composite score for each child’s family was calculated by summing the scores from the three components (income, occupation, and education). Based on the total scores, the socio-economic level of the family was categorized as: low (scores 5–7), medium (scores 8–10), and high (scores 11–17) [10].
Outcomes
The primary endpoint was all-cause mortality, which was defined as death from any cause occurring after hospital discharge. Unplanned readmission was defined as admission to a healthcare facility for any unforeseen reason during the follow-up period. Adverse events included CAV and PTLD. CAV was diagnosed either by myocardial tissue biopsy or through imaging examinations. Cases of PTLD were identified by reviewing all histopathology reports from children who participated in the study.
Statistical analysis
Data normality tests were conducted for each continuous variable to assess their distribution. The summary statistics are presented as median (IQR) or number (%). To compare the characteristics of patients with different socio-economic statuses, the Kruskal-Wallis test was used for continuous variables, while the χ² test was employed for categorical variables. Survival estimates for patients discharged alive were calculated using the Kaplan-Meier method. The log-rank test was used to compare the survival rates among patients with different socio-economic statuses. Additionally, the interaction between socio-economic status and other factors was evaluated using multivariate Cox models. Multivariable Cox proportional hazard regression models were utilized to estimate hazard ratios (HRs) and 95% confidence intervals (95%CI) for the association between socio-economic status (low versus high, medium versus high) and the prognosis for all-cause mortality.Variables considered clinically relevant at baseline or with P<0.20 in the univariate model were entered into multivariate Cox models. Additionally, the number of unplanned readmissions, insurance claims, and cardiac outpatient visits were also compared across socio-economic status. All statistical analyses were performed with SPSS Statistics 24.0 software (IBM Corp, Armonk, NY, USA). Data were plotted using the GraphPad Prism program (version 8.0; GraphPad).
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