Management of allosensitized cardiac transplant candidates
Section snippets
Background
Cardiac transplantation has evolved over the last several decades to become the best available therapy in select patients with advanced heart failure with a high probability of death. The evolution in the field has been propelled by the development of newer, more effective immunosuppressive agents that decrease the likelihood of acute cellular rejection and increase post-transplantation survival while having modest effects on the incidence of infection and malignancy after transplantation.
Detection of anti-HLA antibodies
Histocompatibility testing identifies appropriate donor-recipient pairs to achieve successful transplantation. Pretransplantation crossmatching identifies recipient serum antibodies that react with donor antigens, a condition that defines the concept of allosensitization. It is critically important to determine whether these antibodies may increase the risk of post-transplantation adverse outcomes, as is the case with anti-HLA immunoglobulins [7].
Screening for allosensitization through the
Allosensitization by exposure to foreign antigens
Commonly recognized risk factors for allosensitization in all transplant candidates include previous allografts, blood product transfusions, and pregnancy [5]. As explained above, the use of VADs as a bridge to transplantation has also been recognized as a risk factor for allosensitization resulting in an increased PRA [25], [26]. The most frequent cause of allosensitization before cardiac transplantation is previous blood transfusions. With the increasing number of older patients who have
Management of allosensitized cardiac transplant candidates
The management of allosensitized cardiac transplant candidates presents steep challenges for transplantation cardiologists and surgeons. The differences in specificity of different antibody-detection techniques, the uncertainty about which antibody specificities are relevant, and the incomplete understanding of B-cell immunity in allotransplantation make solid progress in this area difficult. There is limited available literature on strategies to treat allosensitization in cardiac transplant
Clinical outcomes in allosensitized cardiac transplant candidates
Pretransplantation allosensitization increases the likelihood of AMR and CAV and decreases overall allograft survival (Fig. 6) [3], [15], [16], [51], [52], [53]. The relationship between anti-HLA antibodies before transplantation and the development of these conditions is well recognized, emphasizing the importance of proper PRA screening and assignment of appropriate donor-recipient matches.
The importance of de novo anti-HLA antibodies after cardiac transplantation
Despite advances in immunosuppressive therapy, the incidence of acute AMR and CAV continues to limit long-term outcomes [54], [76]. A study by Rose et al [77] demonstrated that the presence of anti-HLA antibodies after cardiac transplantation results in lower survival when compared with being antibody-free. At 5 years after transplantation, survival in the antibody-negative group was 90% compared with 53% in the antibody-positive group. Acute rejection and infection, partly related to augmented
Conclusions
Cardiac transplantation has become the best available therapy in select patients with advanced heart failure with a high probability of death. However, an inadequate number of available hearts remains rate-limiting in the provision of transplantation to those in need, leading to longer wait-list times for many transplant candidates, with a potential for higher wait-list mortality.
In view of the limited donor pool, mechanical circulatory support with VADs was introduced as a bridge to
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