The field of heart transplantation continues to evolve, with major changes in allocation systems and the increasing use of extended-criteria donor hearts, including hearts from donation after circulatory death donors, hearts supported with ex-vivo perfusion, and hearts from hepatitis C viremic donors. The use of such non-traditional donor hearts has made transplantation available to a larger number of recipients, but the demand continues to outpace the supply. Given this persistent donor heart shortage, much attention has been paid to the topic of donor-recipient size matching. Prior studies have challenged traditional criteria for size matching, 1-3 while others have attempted to identify the optimal metric for matching donor and recipient heart size by comparing criteria, such as height, weight, body mass index (BMI), body surface area (BSA), and predicted heart mass (PHM). [4][5][6][7] This 36th annual adult heart transplant report is based on data submitted to the International Society for Heart and Lung Transplantation (ISHLT) Thoracic Organ Transplant Registry on 146,975 heart transplants in recipients of all ages (including 131,249 adult heart transplants)

This year marks the 50th anniversary of the first heart transplant, performed in 1967. Since then, and in particular since the introduction of cyclosporine immunosuppression in the 1970s, heart transplantation has grown worldwide. This 34th adult heart transplant report is based on data submitted to the International Society for Heart and Lung Transplantation (ISHLT) Registry on 135,387 heart transplants in recipients of all ages (including 120,991 adult heart transplants) through June 30, 2016. With each year's report we now also provide more detailed analyses on a particular focus theme. Since 2013, these have been donor and recipient age, retransplantation, early graft failure, indication for transplant, and in 2017, allograft ischemic time. Statistical methods Data collection, conventions and statistical methods National and multinational organ/data exchange organizations and individual centers submit data to the ISHLT

This 36 th adult lung and heart-lung transplant report summarizes data from 69,200 adult lung and 4,128 adult heart-lung transplants performed through June 30, 2018 and reported to the International Thoracic Organ Transplant Registry. With each year's report, we now provide more detailed analyses on a particular focus theme important to patient outcomes. Since 2013, these have been donor and recipient age; retransplantation; early graft failure; indication for transplant; allograft ischemic time; and multiorgan transplantation. Although widely accepted as critical to decision making at the time of receipt of an organ donor offer, there is surprisingly little literature outlining current practice and the impact of size (mis-)matching on outcomes. Hence, this year's report focuses on an overall theme of donor and recipient size matching. In addition to reporting donor and recipient height and weight difference for all adult lung and heart-lung transplant recipients stratified by transplant type (bilateral or single) and indication, we report historical trends and associations between size match and survival. The Registry's online slide sets include results from additional analyses and complementary information not included in this publication (see https:// ishltregistries.org/registries/slides.asp).

Summary There are few substantive methods to measure the health of the immune system, and the connection between immune strength and the viral component of the microbiome is poorly understood. Organ transplant recipients are treated with a post-transplant therapy that combines immunosuppressive and antiviral drugs, offering a window into the effects of immune modulation on the virome. We used sequencing of cell-free DNA in plasma to investigate drug-virome interactions in a cohort of organ transplant recipients (656 samples, 96 patients), and find that antivirals and immunosuppressants strongly affect the structure of the virome in plasma. We observe marked virome compositional dynamics at the onset of the therapy and find that the total viral load increases with immunosuppression, whereas the bacterial component of the microbiome remains largely unaffected. The data provide insight into the relationship between the human virome, the state of the immune system, and the effects of pharmacological treatment, and offer a potential application of the virome state to predict immunocompetence.

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Monitoring allograft health is an important component of posttransplant therapy. Endomyocardial biopsy is the current gold standard for cardiac allograft monitoring but is an expensive and invasive procedure. Proof of principle of a universal, noninvasive diagnostic method based on high-throughput screening of circulating cell-free donor-derived DNA (cfdDNA) was recently demonstrated in a small retrospective cohort. We present the results of a prospective cohort study (65 patients, 565 samples) that tested the utility of cfdDNA in measuring acute rejection after heart transplantation. Circulating cell-free DNA was purified from plasma and sequenced (mean depth, 1.2 giga–base pairs) to quantify the fraction of cfdDNA. Through a comparison with endomyocardial biopsy results, we demonstrate that cfdDNA enables diagnosis of acute rejection after heart transplantation, with an area under the receiver operating characteristic curve of 0.83 and sensitivity and specificity that are comparable to the intrinsic performance of the biopsy itself. This noninvasive genome transplant dynamics approach is a powerful and informative method for routine monitoring of allograft health without incurring the risk, discomfort, and expense of an invasive biopsy.

The survival rate following lung transplantation is among the lowest of all solid-organ transplants, and current diagnostic tests often fail to distinguish between infection and rejection, the two primary posttransplant clinical complications. We describe a diagnostic assay that simultaneously monitors for rejection and infection in lung transplant recipients by sequencing of cell-free DNA (cfDNA) in plasma. We determined that the levels of donor-derived cfDNA directly correlate with the results of invasive tests of rejection (area under the curve 0.9). We also analyzed the nonhuman cfDNA as a hypothesis-free approach to test for infections. Cytomegalovirus is most frequently assayed clinically, and the levels of CMV-derived sequences in cfDNA are consistent with clinical results. We furthermore show that hypothesis-free monitoring for pathogens using cfDNA reveals undiagnosed cases of infection, and that certain infectious pathogens such as human herpesvirus (HHV) 6, HHV-7, and adenovirus, which are not often tested clinically, occur with high frequency in this cohort.organ transplantation | cell-free DNA | infection | rejection | diagnosis

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