Since its inception however, the challenge has been to balance immunosuppression so as to minimize allograft rejection, drug toxicity, infection, and malignancy. transplantation was however limited by the lack of adequate immunosuppressive therapy, failure to monitor for allograft rejection, and unacceptable infection rates leading to high transplant mortality. The development of the percutaneous method for acquiring endomyocardial biopsies (EMB) for the assessment of rejection was a major step forward in post-transplant management , and this technique has survived the test of time over the last 45?years. Initial interpretation was limited to evaluation of acute cellular rejection (ACR), but in recent years, there has been increasing appreciation for the role of donor-specific antibody causing acute antibody-mediated rejection (AMR), a diagnosis associated with potentially worse outcomes than ACR . While histologically its diagnosis has been more challenging, in recent years, a consensus has evolved regarding its interpretation on EMB . However, despite its ubiquitous use, the EMB remains with significant limitations. Its invasive nature is associated with procedural pain and finite Lithospermoside complication risk including tricuspid valve injury , myocardial perforation  and development of coronary fistula . The technique also has limited sensitivity due to sampling error, failure to assess deeper myocardial tissue, and lack of agreement in histological interpretation even between experienced pathologists . The biopsy however remains the gold standard for surveillance and diagnosis of acute rejection. Most programs continue to use this as the primary method for Lithospermoside surveillance for the first 6C12?months, although the introduction of gene expression profiling (GEP) (see below) has reduced the number of biopsies needing to be performed in many patients. Patients at high risk for rejection, particularly AMR, should continue to be monitored by EMB in the first year. After the first postoperative 12 Lithospermoside months, EMB surveillance for an extended period of time (e.g., every 4C6?months) is recommended in heart transplant recipients at higher risk for late acute rejection to reduce the risk for rejection with hemodynamic compromise and the risk of death in black recipients who are at higher risk for rejection. A typical first-year protocol for EMBs is usually layed out in Fig.?1a (EMB Protocol) for patients being maintained indefinitely on long-term corticosteroids. In patients being considered to be weaned off corticosteroids, this may be performed as early as 8C12?weeks post-transplant in appropriately selected patients, but most programs will defer until the sixth month. Open in a separate windows Fig. 1 Common surveillance protocols for allograft rejection for the first 12?months after heart transplantation (Tx) More recently, molecular techniques have been evaluated to determine whether gene expression profiles within Lithospermoside the myocardium on a biopsy can improve diagnostic yields . A microarray-based system has been developed to assess EMB specimens (The Molecular Microscope?). Artificial intelligence techniques using principal component analysis and archetype analysis of rejection-associated transcripts decided in kidney transplants Rabbit Polyclonal to FGB to be associated with AMR or ACR or both was assessed in EMBs and compared with both histological diagnoses and presence of donor-specific antibody. The initial experience is highly favorable with the test being able to estimate the probability and distinguish AMR from ACR. Loupy further decided unique transcripts associated with AMR, including natural killer cell transcripts, macrophage transcripts, endothelial activation transcripts, and interferon gamma transcripts correlating closely with histological International Society of Heart and Lung Transplantation (ISHLT) pathology antibody mediated rejection (pAMR) grades . This technology raises the potential to make a rejection diagnosis from a single biopsy core, improve histology systems, open the potential for automation, and provide quantitative results. It may also provide insights into pathologic processes and a personalized medicine approach to therapies. While these improvements show promise in increasing the diagnostic yield of the EMB, the search for a noninvasive blood-based test to assess allograft rejection remains very attractive, potentially reducing cost and complications and allowing more frequent screening to assess response to anti-rejection therapy. Donor-specific antibodies Both the presence of donor specific antibodies (DSA) at the time of transplant and the development of de novo DSA after transplant Lithospermoside have been associated with adverse post-transplant outcomes, including rejection, cardiac allograft vasculopathy, and graft loss [10, 11]. However, even though DSA may be seen in up to.