Human Leukocyte Antigen-DR Mismatch Is Associated With Increased In-Hospital Mortality After a Heart Transplant

Abstract

Objectives: Although previous studies have investigated the effect of human leukocyte antigen matching on long-term outcomes after heart transplants, its role in the prognosis after a heart transplant remains unclear, particularly with respect to short-term survival.

Further evidence on HLA‐DR matching in determining heart transplantation outcomes

“…In this regard, the above study [1] was conducted in a very long window of observation time (i.e., 1984–2016) and, thus, with an evident difference in immunosuppressive drug regimens and potential bias of the study results. However, since our multidisciplinary group has more than 35 years of experience in heart trasplantation [3,4,6–9], we retain the scientific conclusions of the study [1] convincing and in line with published studies [2–5] but we believe that the topic should be addressed by large registries analyses to gain more granular differences taking account of the role of induction therapy, different primary (CYA vs. Tac) immunosuppressant, or antiproliferative drugs. We should keep in mind the HLA‐DR mismatch during allocation in a clinical environment in which, implementing new technologies of graft preservation (ex situ organ perfusion), mechanisms of organ exchange (also transborder) – similar to the kidney exchange programs used for the living donations – could permit to allocate the right graft aiming to save the life of the recipient during the short term, but also aiming to lower the immunosuppressive burden and the best long‐term organ preservation.…”

“…Preliminary data from these findings were presented annually both at the European Society of Organ Transplantation (ESOT) and the European Society of Cardiology (ESC) between 2012 and 2018. None of these studies [2][3][4][5] were quoted by Osorio-Jaramillo et al [1]. Overall, the "take-home" message of these papers is similar; in fact, all studies declared that HLA-DR mismatch is associated with worse prognosis in heart transplant.…”

“…Although they analyzed the role of mismatch at level of epitopes [1], the original idea that HLA‐DR mismatching would correlate with early cardiac allograft rejection and graft survival was hypothesized in the early 90’ [2]. Besides, our group published in 2013 [3] the evidence that HLA‐DR mismatch was associated with increased in‐hospital mortality after a heart transplant in 158 consecutive patients who had undergone a heart transplant between 2000 and 2008. More recently, we [4] and another group [5] have published the long‐term effects of HLA‐DR Matching on outcomes after heart transplantation.…”

“…Overall, the “take‐home” message of these papers is similar; in fact, all studies declared that HLA‐DR mismatch is associated with worse prognosis in heart transplant. One major concern of the Reviewers of our first paper [3] was the long window of our observation (i.e., 2000–2008) which may affect outcomes due to diverse immunosuppressive regimens. In this regard, the above study [1] was conducted in a very long window of observation time (i.e., 1984–2016) and, thus, with an evident difference in immunosuppressive drug regimens and potential bias of the study results.…”

The Man with 2 Hearts: 25 Years from Heterotopic to Orthotopic Heart Transplantation

“…16 The effects of HLA-A and -B mismatches seemingly manifest themselves primarily in the short term (within 1 yr of transplantation), whereas DR mismatch is thought to contribute most to the number and severity of rejection episodes in the long term, in addition to higher in-hospital mortality rates. 17,18 An HLA mismatch has also been implicated in graft vasculopathy. Despite the limitations of the studies designed to clarify the relationship between poor histocompatibility and vasculopathy, multiple rejection episodes, particularly beyond the first year after transplantation, have been correlated with cardiac allograft vasculopathy.…”