GENETIC BIOMARKERS OF ACUTE GRAFT REJECTION AFTER HEART TRANSPLANTATION
Introduction
Heart transplantation has profoundly impacted the management of end-stage heart disease, offering renewed life to patients with otherwise limited treatment options. The journey began with the world's first successful human heart transplant by Dr. Christiaan Barnard in 1967, a monumental event that paved the way for the procedure's future developments [4,8,34]. In Kazakhstan, for the first time, a heart transplant was performed on August 8, 2012 [26]. Heart transplantation (HT) has become an established therapy for patients with heart failure (HF), representing the gold-standard treatment for end-stage HF [30]. Thus, in Kazakhstan, the prevalence of HF dramatically increased from 4393 to 22,088 people per million population during the 2014-2021 years [65]. It is worth noting that age-standardized CVD mortality rates among countries in Central Asia ranged from 331.8 to 542.3 per 100,000 in 2022. Of the 21 regions, Central Asia ranked 4th in 1990 and 2nd in 2022 for age-standardized CVD mortality, and 1st in CVD age-standardized prevalence in 2022. Moreover, epidemiologically, it addresses the high burden of cardiomyopathies and ischemic heart disease prevalent in the region [40,64].
Due to limited donor supply, a decline in the number of HTs was observed between the 1990s and early 2000s; however, in recent years, the number of HT patients has increased, and about 5500 HTs have been performed annually worldwide in recent years [39]. Since then, advancements in surgical techniques and immunosuppressive therapy have significantly improved patient outcomes. The introduction of drugs like cyclosporine has been pivotal in reducing graft rejection and enhancing survival rates. The median lifespan following adult heart transplants conducted from 2002 to 2009 is approximately 12.5 years, with an extension to about 14.8 years among those who survive the first year after transplantation [30]. Advances in immunosuppression and patient management have led to significant improvements in survival, with one-year post-transplant survival rates now exceeding 80%, and substantial increases in longer-term survival [37,51]. Survival rates within the first year after a heart transplant and overall longevity differ based on the initial diagnosis. For example, individuals receiving transplants due to nonischemic and ischemic cardiomyopathies exhibit the highest survival rates after one year, whereas those undergoing retransplantation show the lowest. As expected, older recipients tend to have shorter long-term survival rates, and older donor ages correlate with increased mortality rates shortly after transplantation. Moreover, female recipients have consistently demonstrated longer median survival compared to male recipients, with women averaging 12.2 years and men 11.4 years [30]. Currently, the one-year survival rate approximates 90%, the five-year survival reaches around 70%, yet the 20-year survival drops to about 20% [2].
HT has significantly advanced, yet it is associated with various complications that can affect the outcomes and quality of life post-surgery. HT patients are at risk of developing various complications during their follow-up. Common complications include early allograft failure, acute graft rejection (AGR), CAV, renal failure, infections, and cancer [2]. The most immediate surgical issues post-transplant can include primary graft failure and complications from the surgical procedure itself. Acute kidney injury is a notable complication, particularly affecting those undergoing more extensive surgeries such as valve replacements or aortic surgeries. This can significantly impact in-hospital mortality and long-term outcomes [21]. Graft rejection remains a primary concern, with both acute and chronic forms. Acute cellular rejection, which is more common in the first six months post-transplant, involves T cell-mediated attacks against the donor heart. Chronic rejection, often manifested as cardiac allograft vasculopathy, involves the slow narrowing of the heart's arteries, which can lead to heart failure or arrhythmias [9]. CAV is a leading cause of long-term graft dysfunction and graft loss after heart transplantation. While CAV pathogenesis is complex, and involves both alloimmune and nonimmune processes, it is apparent that both donor and recipient risk factors predispose to CAV development [31].
Recent advancements in the field of HT include the development of new immunosuppressive agents that show promise in reducing the incidence of acute rejection and improving overall graft survival. Additionally, techniques in donor heart preservation and novel monitoring methods for rejection [9]. Therefore, it is crucial to establish an effective follow-up protocol for HT patients’ right from the early post-transplant stages [45].
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Bibliography link
Bayanova M., Askerbekova A., Nazarova L., Abdikadirova A., Sapargaliyeva M., Malik D., Myrzakhmetova G., Pya Yu., Bolatov A. Genetic biomarkers of acute graft rejection after heart transplantation // Nauka i Zdravookhranenie [Science & Healthcare]. 2024. Vol.26 (4), pp. 177-189. doi 10.34689/SH.2024.26.4.021Related publications:
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