黑料网

Heart transplantation; Orthotopic transplantation; Heterotopic transplantation; Ischemic time; Immunosuppression; Rejection; Antibody-mediated rejection; Cellular rejection; Tolerance; Mechanical circulatory support

Introduction

Heart transplantation has evolved from an experimental procedure to a well-established therapy for patients with end-stage heart failure, offering improved survival and quality of life [1]. The first successful human heart transplant, performed by Christiaan Barnard in 1967, marked a turning point in cardiac medicine. However, early outcomes were limited by challenges related to surgical techniques, organ preservation, and rejection. Over the subsequent Junades, significant progress has been made in addressing these challenges, leading to substantial improvements in patient outcomes [2].

The standard surgical technique for heart transplantation is orthotopic transplantation, which involves removing the recipient's diseased heart and replacing it with the donor heart in the anatomical position. A less common technique, heterotopic transplantation, involves implanting the donor heart alongside the recipient's native heart, providing circulatory support. This technique is typically reserved for specific situations, such as when the recipient has severe pulmonary hypertension or size mismatch between the donor and recipient hearts [3].

Description

Significant advancements have been made in organ preservation techniques, extending the permissible ischemic time (the time the heart is without blood supply). Improved preservation solutions and hypothermic storage have allowed for longer distances for organ transport and more time for recipient-donor matching [4]. Machine perfusion techniques, which involve perfusing the donor heart with a preservation solution at controlled temperature and pressure, are also being increasingly used to further extend preservation time and assess organ viability.

Immunosuppression remains a cornerstone of heart transplantation, preventing rejection of the donor heart by the recipient’s immune system. The introduction of cyclosporine in the late 1970s revolutionized immunosuppressive therapy, significantly improving early graft survival [5]. Current immunosuppressive regimens typically involve a combination of agents, including calcineurin inhibitors (tacrolimus or cyclosporine), antimetabolites (mycophenolate mofetil), and corticosteroids.

Despite advancements in immunosuppression, rejection remains a significant challenge. Rejection can be broadly classified as cellular rejection, mediated by T lymphocytes, or antibody-mediated rejection (AMR), mediated by antibodies targeting donor antigens [6]. AMR, in particular, is a challenging form of rejection to treat and can lead to rapid graft dysfunction. Monitoring for donor-specific antibodies (DSAs) is crucial for early detection and management of AMR.

Discussion

The development of more targeted immunosuppressive agents and strategies has led to a reduction in the incidence of acute rejection episodes. However, chronic rejection, characterized by progressive graft dysfunction and cardiac allograft vasculopathy (CAV), remains a major cause of late graft loss [7]. CAV, a form of accelerated coronary artery disease affecting the transplanted heart, is a complex process involving both immunological and non-immunological factors.

The use of mechanical circulatory support (MCS) devices, such as left ventricular assist devices (LVADs), has significantly impacted heart transplantation. MCS devices can be used as a bridge to transplantation (BTT), supporting patients with advanced heart failure while they await a suitable donor heart [8]. MCS devices can also be used as destination therapy (DT) for patients who are not candidates for transplantation.

The development of non-invasive methods for monitoring graft health and detecting rejection is an important area of ongoing research. Techniques such as donor-derived cell-free DNA (dd-cfDNA) monitoring and gene expression profiling hold promise for earlier and less invasive detection of rejection [9]. These techniques could potentially reduce the need for routine endomyocardial biopsies, which are invasive and associated with potential complications.

Achieving tolerance, a state of specific unresponsiveness of the immune system to the graft without the need for chronic immunosuppression, remains a major goal in transplantation. Several strategies are being explored to induce tolerance, including costimulatory blockade, regulatory T cell therapy, and mixed chimerism.

Future research in heart transplantation should focus on several key areas. Developing more effective strategies to prevent and treat chronic rejection and CAV is crucial for improving long-term graft survival. Further investigation into the mechanisms of tolerance and the development of reliable tolerance induction protocols are needed to eliminate the need for chronic immunosuppression. The use of artificial intelligence and machine learning to optimize donor-recipient matching and predict transplant outcomes is also a promising area of research [10].

The development of more sophisticated MCS devices and the exploration of new technologies, such as xenotransplantation and tissue engineering, offer potential solutions for addressing the ongoing organ shortage. Personalized immunosuppression strategies based on individual patient characteristics and immune profiles are also likely to play an increasingly important role in improving outcomes.

Conclusion

Significant progress has been made in heart transplantation over the past Junades, leading to improved patient survival and quality of life. Advancements in surgical techniques, organ preservation, immunosuppressive strategies, and pre- and post-transplant management have all contributed to these improvements. However, challenges such as chronic rejection, CAV, and the ongoing organ shortage remain. Continued research and innovation in these areas are essential to further improve outcomes and expand access to this life-saving therapy.

Acknowledgement

None

Conflict of Interest

None

References

1. Delgado JF, Reyne AG, Dios S, López-Medrano F, Jurado A, et al. (2015) Influence of cytomegalovirus infection in the development of cardiac allograft vasculopathy after heart transplantation. J Heart Lung Transplant 3:1112-1119.

Indexed at, Google Scholar, Crossref

2. Raffa GM, Di Gesaro G, Sciacca S, Tuzzolino F, Turrisi M, et al. (2016) Heart transplant program at IRCCS-ISMETT: Impact of mechanical circulatory support on pre- and post -transplant survival. Int J Cardiol 219: 358-361.

Indexed at, Google Scholar, Crossref

3. Zielińska K, Kukulski L, Wróbel M, Przybyłowski P, Rokicka D, et al. (2022) Carbohydrate Metabolism Disorders in Relation to Cardiac Allograft Vasculopathy (CAV) Intensification in Heart Transplant Patients According to the Grading Scheme Developed by the International Society for Heart and Lung Transplantation (ISHLT). Ann Transplant 27: 933420.

Indexed at, Google Scholar, Crossref

4. Conway J, Manlhiot C, Kirk R, Edwards LB, McCrindle BW, et al. Mortality and morbidity after retransplantation after primary heart transplant in childhood: an analysis from the registry of the International Society for Heart and Lung Transplantation. J Heart Lung Transplant 33: 241-51.

Indexed at, Google Scholar, Crossref

5. Vanderlaan RD, Manlhiot C, Edwards LB, Conway J, McCrindle BW, et al. (2015) Risk factors for specific causes of death following pediatric heart transplant: An analysis of the registry of the International Society of Heart and Lung Transplantation. Pediatr Transplant 19: 896-905.

Indexed at, Google Scholar, Crossref

6. Kitamura S (2012) Heart transplantation in Japan: a critical appraisal for the results and future prospects. Gen Thorac Cardiovasc Surg 60: 639-644.

Indexed at, Google Scholar, Crossref

7. Wever-Pinzon O, Edwards LB, Taylor DO, Kfoury AG, Drakos SG, et al. (2017) Association of recipient age and causes of heart transplant mortality: Implications for personalization of post-transplant management-An analysis of the International Society for Heart and Lung Transplantation Registry. J Heart Lung Transplant 36: 407-417.

Indexed at, Google Scholar, Crossref

8. Saczkowski R, Dacey C, Bernier PL (2010) Does ABO-incompatible and ABO-compatible neonatal heart transplant have equivalent survival. Interact Cardiovasc Thorac Surg 10: 1026-1033.

Indexed at, Google Scholar, Crossref

9. Jeewa A, Manlhiot C, Kantor PF, Mital S, McCrindle BW, et al. (2014) Risk factors for mortality or delisting of patients from the pediatric heart transplant waiting list. J Thorac Cardiovasc Surg 147: 462-468.

Indexed at, Google Scholar, Crossref

10. Sivathasan C, Lim CP, Kerk KL, Sim DK, Mehra MR, et al. (2017) Mechanical circulatory support and heart transplantation in the Asia Pacific region. J Heart Lung Transplant 36: 13-18.

Indexed at, Google Scholar, Crossref