Cardiac Graft Assessment in the Era of Machine Perfusion: Current and Future Biomarkers

Heart transplantation remains the treatment of reference for patients experiencing end‐stage heart failure; unfortunately, graft availability through conventional donation after brain death is insufficient to meet the demand. Use of extended‐criteria donors or donation after circulatory death has emerged to increase organ availability; however, clinical protocols require optimization to limit or prevent damage in hearts possessing greater susceptibility to injury than conventional grafts. The emergence of cardiac ex situ machine perfusion not only facilitates the use of extended‐criteria donor and donation after circulatory death hearts through the avoidance of potentially damaging ischemia during graft storage and transport, it also opens the door to multiple opportunities for more sensitive monitoring of graft quality. With this review, we aim to bring together the current knowledge of biomarkers that hold particular promise for cardiac graft evaluation to improve precision and reliability in the identification of hearts for transplantation, thereby facilitating the safe increase in graft availability. Information about the utility of potential biomarkers was categorized into 5 themes: (1) functional, (2) metabolic, (3) hormone/prohormone, (4) cellular damage/death, and (5) inflammatory markers. Several promising biomarkers are identified, and recommendations for potential improvements to current clinical protocols are provided.

Novel Diagnostic and Therapeutic Approach to Antibody-Mediated Rejections in Heart Transplantation

Despite the improvement of immunosuppressive therapy in heart transplantation (HTx), antibody-mediated rejection (AMR) is still a great obstacle to prolong cardiac graft survival. Anti-donor-specific antibodies (DSAs), especially anti-donor human leukocyte antigen (HLA) antibody, lead to heart graft failure resulting in hemodynamic consequence and often in the recipient death. To prevent hyperacute rejection, prospective complement-dependent cytotoxicity test has been performed in every cardiac donor in Japan. But in other solid organ transplantations, flow cytometry crossmatch has been recently recommended to crossmatch to select the recipient in Japan as well as the world. However, flow cytometry is too sensitive to select the recipient, because not all DSAs determined by flow cytometry are cytotoxic to the cardiac graft. On the first complement classical pathway, alloantibodies bind to HLA antigens on cells of the graft and then recruit C1q, which is essential to make membrane attack complex and kill the cell. We review a role of the novel monitoring method of complement pathway regarding C1q in occurrence of AMR and its diagnostic and therapeutic significance in managing AMR in HTx.

Intravascular visualization methods in estimating vasculopathy of a transplanted heart

One of the pathognomonic signs of сardiac allograft vasculopathy is concentric intimal hyperplasia, which can be assessed by intravascular imaging techniques. Early detection of cardiac graft vasculopathy and timely correction of immunosuppressive therapy can help slow the pathological process and, as a result, increase the functional survival of the heart graft. Recently, the method of intravascular optical coherence tomography, which improves the accuracy of the assessment of the layers of the vascular wall and is considered as an alternative to intravascular ultrasound, is becoming more and more common. This review focuses on the importance of modern methods of intravascular imaging in the early diagnosis of cardiac graft vasculopathy and the identification of predictors of this disease.