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We analyzed humoral immune responses to nonhuman leukocyte antigen (HLA) after cardiac transplantation to identify antibodies associated with allograft rejection. Protein microarray identified 366 non-HLA antibodies (>1.5 fold, P < .5) from a discovery cohort of HLA antibody-negative, endothelial cell crossmatch-positive sera obtained from 12 cardiac allograft recipients at the time of biopsy-proven rejection. From these, 19 plasma membrane proteins and 10 autoantigens identified from gene ontology analysis were combined with 48 proteins identified through literature search to generate a multiplex bead array. Longitudinal sera from a multicenter cohort of adult cardiac allograft recipients (samples: n = 477 no rejection; n = 69 rejection) identified 18 non-HLA antibodies associated with rejection (P < .1) including 4 newly identified non-HLA antigenic targets (DEXI, EMCN, LPHN1, and SSB). CART analysis showed 5/18 non-HLA antibodies distinguished rejection vs nonrejection. Antibodies to 4/18 non-HLA antigens synergize with HLA donor-specific antibodies and significantly increase the odds of rejection (P < .1). The non-HLA panel was validated using an independent adult cardiac transplant cohort (n = 21 no rejection; n = 42 rejection, >1R) with an area under the curve of 0.87 (P < .05) with 92.86% sensitivity and 66.67% specificity. We conclude that multiplex bead array assessment of non-HLA antibodies identifies cardiac transplant recipients at risk of rejection., (© 2020 The American Society of Transplantation and the American Society of Transplant Surgeons.)

The infectious disease coronavirus disease 2019 (COVID-19) was declared a pandemic by the World Health Organization in March 2020. The impact of COVID-19 on solid organ transplantations, including heart transplantation, is currently unclear. Many transplant programs have been forced to swiftly re-evaluate and adapt their practices, leading to a marked decrease in transplants performed. This trend has been due to various factors, including increased donor COVID-19 screening scrutiny and recipient waiting list management in anticipation of COVID-19 critical care surge capacity planning. In the face of these unknown variables, determining when and how to proceed with transplantation in our population of patients with end-stage cardiomyopathies is challenging. Here, we describe our center's experience with orthotopic heart transplantation (OHT) in one of the country's pandemic epicenters, where we performed eight OHTs in the first 2 months after community spread began in late February 2020., (© 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Survival after heart transplantation (HTx) is limited by complications related to alloreactivity, immune suppression, and adverse effects of pharmacologic therapies. We hypothesize that time-dependent phenomapping of clinical and molecular data sets is a valuable approach to clinical assessments and guiding medical management to improve outcomes., Methods: We analyzed clinical, therapeutic, biomarker, and outcome data from 94 adult HTx patients and 1,557 clinical encounters performed between January 2010 and April 2013. Multivariate analyses were used to evaluate the association between immunosuppression therapy, biomarkers, and the combined clinical end point of death, allograft loss, retransplantation, and rejection. Data were analyzed by K-means clustering (K = 2) to identify patterns of similar combined immunosuppression management, and percentile slopes were computed to examine the changes in dosages over time. Findings were correlated with clinical parameters, human leucocyte antigen antibody titers, and peripheral blood mononuclear cell gene expression of the AlloMap (CareDx, Inc., Brisbane, CA) test genes. An intragraft, heart tissue gene coexpression network analysis was performed., Results: Unsupervised cluster analysis of immunosuppressive therapies identified 2 groups, 1 characterized by a steeper immunosuppression minimization, associated with a higher likelihood for the combined end point, and the other by a less pronounced change. A time-dependent phenomap suggested that patients in the group with higher event rates had increased human leukocyte antigen class I and II antibody titers, higher expression of the FLT3 AlloMap gene, and lower expression of the MARCH8 and WDR40A AlloMap genes. Intramyocardial biomarker-related coexpression network analysis of the FLT3 gene showed an immune system-related network underlying this biomarker., Conclusions: Time-dependent precision phenotyping is a mechanistically insightful, data-driven approach to characterize patterns of clinical care and identify ways to improve clinical management and outcomes., (Copyright © 2018 International Society for the Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.)

Donors of death due to anoxic brain injury such as suicidal hanging are at risk for a severe catecholamine surge leading to an acute myocardial stress that can cause global tissue hypoxia as well as pulmonary edema and barotrauma, all of which may potentially adversely impact myocardial tissue. Concerns have been raised about potential higher rates of Primary Graft Dysfunction (PGD) in heart transplant recipients of such donors due to this acute myocardial stressor. We wanted to assess if this mechanism of donor death does carry an increased risk of PGD or other adverse outcomes in our single center experience. Between January 2014 and July 2019, 331 heart transplantations were performed at our center. Seventeen patients received a heart from donors after suicidal hanging, confirmed by review of the United Network for Organ Sharing UNet DonorNet database. Three out of 17 recipients (18%) from suicidal hanging donors experienced primary graft dysfunction (PGD) peri-operatively requiring extracorporeal membrane oxygenation (ECMO). In comparison, 29 out of 314 recipients (9%) from all other donors during this time period experienced PGD requiring peri-operative ECMO (p = 0.25). The 30-day and 1-year survival among recipients of grafts from suicidal hanging donors were 16/17 (94%) and 16/17 (94%), respectively. The one death during this period was due to complications from PGD (multi-system organ failure, ischemic limb with ECMO). Overall, in a large-volume, single-center experience, while there was a trend toward a higher incidence of PGD requiring ECMO, transplantation of a heart from a suicidal hanging donor was not associated with a higher 30-day and 1-year mortality. Thus, these results suggest that hearts from suicidal hanging donors may be appropriately considered for transplantations, with heightened awareness of a possible increased risk of PGD requiring ECMO. [ABSTRACT FROM AUTHOR]