Examining a 12-year experience within Kazakhstan’s national heart transplantation program | Scientific Reports – Nature.com

This study consists of two distinct stages: the analysis of HTx program outputs and outcomes. The primary source of data was the Republican Center for Coordination of Transplantation and High-Tech Services, hereafter referred to as the Transplantation Coordination Center, under the Ministry of Health (MoH) of Kazakhstan. Functioning as the national agency providing technical support to all hospitals performing organ transplantations in Kazakhstan, this center is responsible for maintaining the medical information system, specifically the Registry of Donors and Recipients, which encompasses data on donors and recipients for various organ transplantations.

The regulation of organ acquisition and donor management in Kazakhstan is governed by the Transplant Act. This legislation aligns with the principles outlined by the International Society for Heart and Lung Transplantation (ISHLT)9. According to the Act, organs can be donated following brain death by individuals aged 18years and older, provided that they have officially confirmed their willingness for postmortem organ donation during their lifetime. This declaration of intent can be made through the "electronic government" web portal or through a general practitioner. In cases where explicit consent from the individual is not available, organ donation is contingent upon the consent of their family10.

Presently, four hospitals in Kazakhstan conduct HTx, with the National Scientific Cardiac Surgery Center in Astana being the primary facility for the majority of HTx and LVAD implantations nationwide. The other three hospitals undertaking these surgical interventions are the Heart Center Shymkent, the Research Institute of Cardiology and Internal Diseases, and the National Scientific Center of Surgery named after Syzganov. The operations of the Transplantation Coordination Center, including the management of the Registry of Donors and Recipients, are governed by the Ministry of Health's directive11.

The annual nationwide rates of HTx and LVAD implantation were computed per million population (pmp). This involved retrieving the number of HTx and LVAD implantations performed in Kazakhstan from the inception of these procedures in 2012 to the present year (2023) from the Registry. Population figures for Kazakhstan in the respective years were sourced from the Demographic Yearbook, a statistical compilation issued by the Bureau of National Statistics12. The aggregated data encompassing nationwide annual incidences of ischemic heart disease (IHD) and heart valve disease (HVD), along with the pmp rates of HTx and LVAD implantations, were organized in an Excel spreadsheet, indicating the reference year for the statistics.

To augment the findings of our study regarding the rates of HTx and LVAD implantation and to generate forecast projections concerning future healthcare needs in the country, we obtained official statistics on the incidence rates of IHD and HVD in Kazakhstan. These two medical conditions represent the primary indications for HTx and LVAD implantation, in accordance with the national standard of care13. The MoH of Kazakhstan annually publishes a yearbook of national health statistics14. For our research, we retrieved data on the incidence of IHD and HVD spanning the years 1998 to 2022 from this resource. The electronic versions of these yearbooks are freely accessible on the website of the National Research Center for Health Development named after Salidat Kairbekova, and details on studies conducted utilizing this yearbook's information are available elsewhere15.

We downloaded yearbooks covering the period from 1998 to 2022 and extracted precalculated incidence rates of IHD and HVD from the "Health Indicators" subsection. The incidence of IHD specifically pertains to adults, defined as individuals aged 18years and older, and is presented per 100,000 people. Similarly, the incidence of HVD is based on the total population, encompassing both adults and children, and is also presented per 100,000 people.

The Expert Modeler function of SPSS was employed to automatically identify the best-fit epidemiological models for each type of predictive analysis: incidence rates of IHD and HVD, as well as pmp rates of HTx and LVAD implantation until 2030. The observed incidences from 1998 to 2022 were utilized for IHD and HVD, while the observed rates for HTx and LVAD implantation from 2012 to 2023 were employed. All projections were reported as estimates along with their 95% confidence intervals (CIs), and corresponding graphs were generated. The significance level for the best-fit epidemiological models was set at 0.05.

The cumulative figures of all adult and pediatric patients awaiting heart transplantation across Kazakhstan's regions from the inception of the program to the end of 2023 were entered into an Excel spreadsheet. The population data for each region of Kazakhstan were acquired from the website of the Bureau of National Statistics to calculate the pmp rates16. To visualize regional variations in the rates of patients awaiting HTx, the Quantum Geographic Information System (QGIS) Version 3.26 "Buenos Aires" was used.

Survival analysis was conducted to evaluate the outcome parameters of the national HTx program. Data on all HTx patients in Kazakhstan were acquired in a fully anonymized manner from the Transplantation Coordination Center. The dataset retrieved from the Registry for HTx patients included various details, such as the date of the HTx procedure, date of death (if applicable), age and sex, blood group and rhesus D (RhD) factor, as well as the weight and height of both the donor and recipient. The inclusion of the latter two variables facilitated the calculation of body mass index (BMI) using the following formula: weight in kilograms divided by height in meters squared. Additionally, information on the cause of death of heart donors was obtained from the registry. Currently, brain death serves as the sole parameter for organ acquisition10, and the causes of donor death are categorized into four broad groups: ischemic stroke, hemorrhagic stroke, brain injury, and neoplasm.

For heart recipients, more extensive data were available, including laboratory values before HTx surgery, such as hemoglobin, creatinine, glomerular filtration rate (GFR), total bilirubin, lactate dehydrogenase, sodium, potassium, white blood cell count, and C-reactive protein. Information related to previous cardiac surgeries, as well as coexisting pathologies such as arterial hypertension, hypothyroidism, pulmonary hypertension, and the type of cardiomyopathy, was also obtained from the registry. In addition, information on the length of postoperative hospital stay and postsurgical morbidity [infection/sepsis, rejection within hospital stay, hemodialysis, resternotomy, and extracorporeal membrane oxygenation (ECMO)] was available and extracted from the registry.

Life tables, KaplanMeier analysis (KM analysis), and Cox regression were the three survival analysis methods employed in this study. The data sourced from the registry were organized in Excel spreadsheets, with the primary variables being the date of HTx, the date of death, or the conclusion of the follow-up period (30th November 2023). Given the unavailability of precise causes of death for HTx patients, overall survival was reported.

Life tables were generated to estimate cumulative survival at specific time intervals: 30days, 90days, 180days, 360days, 720days, 1080days, 1380days, and 1740days. The number of patients who survived and those who died at the end of each interval was documented. Cumulative mortality rates were calculated using the following formula: 100 cumulative survival.

KM analysis was employed to assess the probability of surviving until the end of the follow-up, along with the mean and median survival of HTx patients, presented with 95% CIs. Since the cumulative survival at the end of the follow-up was 58.1%, only the mean survival time was reported. A graph depicting the overall survival curve during the study period was generated.

Multivariate Cox regression analysis was employed to assess the risk factors associated with mortality among HTx patients. The selection of factors was based on their independence from each other. These factors were categorized into two main groups, donor-related and recipient-related, and their respective effects were reported separately. The donor-related factors included age, sex, weight, height, blood group, RhD factor, and cause of death. Recipient-related factors were further subdivided into three categories: presurgical factors (such as age, sex, weight, height, blood group, RhD factor, history of previous cardiac surgeries including LVAD implantation, arterial hypertension, hypothyroidism, pulmonary hypertension, and type of cardiomyopathyischemic, dilated, or valvular), presurgical laboratory values (including hemoglobin levels (g/L), creatinine levels (mg/dL), GFR (mL/min), total bilirubin levels (mg/dl), lactate dehydrogenase levels (U/L), sodium levels (mmol/L), potassium levels (mmol/L), white blood cell count, and C-reactive protein levels (mg/L)), and postsurgical factors (such as length of postoperative hospital stay and postsurgical morbidity including infection/sepsis, rejection within hospital stay, requirement for hemodialysis, resternotomy, and ECMO). Adjusted hazard ratios (HRs) were computed for all variables, and the statistical significance level of the Cox regression model was set at 0.05. Survival analysis was performed using the "Survival" function in the Statistical Package for Social Sciences (SPSS) version 24.0 for Windows.

This study was conducted in strict accordance with the principles outlined in the Helsinki Declaration. Only completely anonymized data obtained from the Transplantation Coordination Center were analyzed. Prior to commencing the data collection, approval was obtained from the Local Commission on Bioethics of the Corporate Fund University Medical Center (hereafter referred to as the Ethics Committee). The Ethics Committee reviewed the case and waived the need for informed consent, as documented in the Minutes of the meeting of Ethics Committee #3 dated July 14, 2023.

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Examining a 12-year experience within Kazakhstan's national heart transplantation program | Scientific Reports - Nature.com