Heart transplantation for patients with end-stage heart failure refractory to medical therapy has remained definitive treatment with significant advances in posttransplant care. Despite improvement in postoperative morbidity and mortality, acute cellular rejection (ACR) and antibody-mediated rejection (AMR) remain substantial challenges that can lead to allograft failure and patient mortality. Immunosuppressive agents have been the mainstay of both prevention and treatment for ACR and AMR; however, many challenges exist with traditional therapies. There are a multitude of molecular pathways involved in mediating the humoral and cellular response to rejection, offering various targets for treatment. This review summarizes therapies used in the management of ACR and AMR as extrapolated from use in induction therapy and treatment of other solid-organ transplant rejection. Future studies focused on cardiac transplant recipients are needed to expand therapeutic options.
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http://dx.doi.org/10.1097/CRD.0000000000000596 | DOI Listing |
J Heart Lung Transplant
December 2024
Clinical and Translational Research in Cardiology Unit, Health Research Institute Hospital La Fe (IISLaFe), Valencia, Spain; Center for Biomedical Research Network on Cardiovascular Diseases, Madrid, Spain. Electronic address:
Background: Liquid biopsy offers a potential alternative to decrease or eliminate endomyocardial biopsy for diagnosing allograft rejection. p-element-induced wimpy testis-interacting RNAs (piRNAs) are novel and promising disease biomarkers for their intrinsic characteristics such as stability in body fluids; however, their role in allograft rejection remains unexplored.
Methods: A training set based on small RNA sequencing technology was performed to identify piRNAs in endomyocardial tissue (n = 8) and serum samples (n = 40) from patients following heart transplantation.
Transplantation
December 2024
Inova Schar Heart and Vascular, Falls Church, VA.
Background: Proteomic phenotyping can provide insights into rejection pathophysiology, novel biomarkers, and therapeutic targets.
Methods: Within the prospective, multicenter Genomic Research Alliance for Transplantation study, 181 proteins were evaluated from blood drawn at the time of endomyocardial biopsy; protein fold change, logistic regression, and pathway analyses were conducted, with protein discovery adjusted for a 5% false discovery rate.
Results: Among 104 adult heart transplant patients (31% female sex, 53% Black race, median age 52 y), 74 had no rejection, 18 developed acute cellular rejection (ACR), and 12 developed antibody-mediated rejection (AMR).
J Heart Lung Transplant
November 2024
Department of Cardiology, Cedars-Sinai Smidt Heart Institute, Los Angeles, California. Electronic address:
Background: Primary graft dysfunction (PGD) remains the leading cause of 30-day mortality post-heart transplantation (HTx). HTx recipients experiencing severe PGD have been found to have high levels of circulating proteins associated with PGD occurrence and post-HTx survival. Whether treating these patients with therapeutic plasma exchange (TPE) can attenuate ongoing immunological and inflammatory processes and improve post-transplant outcomes has not been well-investigated.
View Article and Find Full Text PDFBiomedicines
October 2024
Department of Cell Biology, George Emil Palade University of Medicine, Pharmacy, Science and Technology of Targu Mures, 540139 Targu Mures, Romania.
Background: Heart transplantation (HT) remains the ultimate treatment for end-stage heart failure. An endomyocardial biopsy (EMB) is "the gold standard" diagnostic procedure used in HT rejection surveillance. The aim of this study is to provide a detailed analysis of the histopathological characteristics of the EMB and to investigate if there is a correlation between some histopathological changes, such as fibrosis, vasculitis, Quilty effect (Q.
View Article and Find Full Text PDFJ Heart Lung Transplant
October 2024
Heart Failure, MCS and Transplant, Inova Schar Heart and Vascular, Falls Church, Virginia. Electronic address:
Background: There is significant variability among pathologists in the histopathological interpretation of the endomyocardial biopsy (EMB) for acute cellular rejection (ACR), and assessment of variability in the interpretation of antibody-mediated rejection (AMR) has not been reported. In contemporary practice, the strategy of allograft surveillance with donor-derived cell-free DNA (dd-cfDNA) compared to EMB has not been compared with a focus on long-term clinical outcomes beyond acute rejection (AR).
Methods: The Genomic Research Alliance for Transplantation is a multicenter, prospective cohort study that enrolled patients from 2015 to 2020.
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