Mehra, Mandeep R.

BACKGROUND: A preservation system, the Organ Care System (OCS; TransMedics) uses normothermic pulsatile perfusion during organ transport for heart transplantation. This system has demonstrated favorable outcomes in hearts recovered from extended-criteria donors after brain death (DBD) and donors after circulatory death (DCD). METHODS: The OCS Heart Perfusion Registry collects data on US heart transplantations using the OCS, static cold storage (SCS), or thoracoabdominal normothermic regional perfusion (NRP) and donor hearts recovered from DBD or DCD donors. We analyzed donor and recipient characteristics and posttransplantation outcomes in patients transplanted with OCS donor hearts (either DBD or DCD) compared with SCS hearts, and with OCS hearts from DCD donors compared with those recovered with NRP followed by SCS. Propensity score matching was used in survival analyses to adjust for differences among recipient characteristics. RESULTS: Between 2021 and 2023, 3225 consecutive heart transplantations enrolled from 56 centers were analyzed in the Heart Perfusion Registry. The OCS was used in 854 of 3225 heart transplantations (26.4%), among which 340 (39.8%) were DBD and 514 (60.2%) were DCD donors, whereas 2174 DBD donors were recovered with SCS and another 197 DCD donors with NRP techniques. The OCS-DBD group experienced a greater number of organ offer refusals before final acceptance (13 versus 6; Wilcoxon rank sum, P <0.001) and a longer transport distance (667 miles versus 232 miles; Wilcoxon rank sum, P <0.001) compared with SCS-DBD. Survival at 12 months was similar between the 2 groups (89.9% for OCS-DBD versus 90.6% for SCS-DBD; marginal Cox model, P =0.54). Among the OCS-DCD and SCS-DBD groups, survival at 12 months was also similar (91.0% versus 92.5%, respectively; marginal Cox model, P =0.32). The OCS-DCD and NRP-DCD groups demonstrated similar survival (91.0% versus 91.7%, respectively; log rank, P =0.63), although the transport distance was longer in OCS-DCD compared with DCD with NRP followed by SCS (400 miles versus 223 miles; Wilcoxon rank sum, P <0.001). By 2023, 90% of all OCS donor management and recovery was performed with dedicated organ recovery teams. CONCLUSIONS: We demonstrate that real-world implementation of the OCS for DBD donors (using predominantly a dedicated recovery team) is associated with expanded donor criteria, longer transport distance, and excellent posttransplantation outcomes. In OCS-DCD donors, outcomes parallel those of donors recovered with NRP-DCD and compare favorably with DBD donor organs.

Abstract Endomyocardial biopsy (EMB) is an invasive procedure, globally most often used for the monitoring of heart transplant (HTx) rejection. In addition, EMB can have an important complementary role to the clinical assessment in establishing the diagnosis of diverse cardiac disorders, including myocarditis, cardiomyopathies, drug-related cardiotoxicity, amyloidosis, other infiltrative and storage disorders, and cardiac tumours. Improvements in EMB equipment and the development of new techniques for the analysis of EMB samples have significantly improved diagnostic precision of EMB. The present document is the result of the Trilateral Cooperation Project between the Heart Failure Association of the European Society of Cardiology, the Heart Failure Society of America, and the Japanese Heart Failure Society. It represents an expert consensus aiming to provide a comprehensive, up-to-date perspective on EMB, with a focus on the following main issues: (i) an overview of the practical approach to EMB, (ii) an update on indications for EMB, (iii) a revised plan for HTx rejection surveillance, (iv) the impact of multimodality imaging on EMB, and (v) the current clinical practice in the worldwide use of EMB.

Objectives: This report summarizes a collaborative effort between the American Society of Reconstructive Transplantation and the International Society of Vascularized Composite Allotransplantation to establish what is known about chronic rejection in recipients of vascularized composite allografts, with an emphasis on upper extremity and face transplants. As a picture of chronic rejection in hand and face vascularized composite allografts emerges, the results will be applied to other types of vascularized composite allografts, such as uterine transplantation. Methods: The overall goal is to develop a definition of chronic rejection in vascularized composite allografts so that we can establish longitudinal correlates of factors such as acute rejection, immunosuppressive therapy, de novo donor-specific antibody and trauma/infection and other external factors on the development of chronic rejection. As Dr Kanitakis eloquently stated at the 2017 International Society of Vascularized Composite Allotransplantation meeting in Salzburg, “Before we can correlate causative factors of chronic rejection, we have to define what chronic rejection in VCA is.” Results: The first meeting report was presented at the sixth Biennial meeting of the American Society of Reconstructive Transplantation in November 2018. Based on collaborative efforts and descriptions of clinical cases of chronic rejection in vascularized composite allograft recipients, a working definition of chronic rejection in vascularized composite allografts with respect to overt functional decline, subclinical functional decline, histologic evidence without functional decline, and normal allograft function in the absence of histologic evidence of chronic rejection is proposed. Conclusions: It is the intent of this collaborative working group that these working definitions will help to focus ongoing research to define the incidence, risk factors and treatment regimens that will identify mechanisms of chronic rejection in vascularized composite allografts. As with all good research, our initial efforts have generated more questions than answers. We hope that this is the first of many updates.

Background:It has been well documented that each additional line of treatment is associated with lower rates of deeper responses, shorter duration of treatment, and increased rates of toxicities/comorbidities in patients with multiple myeloma (MM; Yong K, et al. Br J Haematol 2016. 175[2]:252–264). These factors contribute to treatment discontinuation and impact the proportion of patients reaching subsequent lines of therapy.Aims:To characterize the rate of therapy attrition at relapse for patients with newly diagnosed MM (NDMM) who are transplant eligible in the United States.Methods:Patients with NDMM were identified from 3 US patient‐level data sources: the OPTUM™ Commercial Claims database (period: January 2000–March 2017), the OPTUM™ Electronic Medical Records (EMR) database (period: January 2007–March 2016), and the Surveillance, Epidemiology, and End Results (SEER)‐Medicare Linked database (period: January 2007–December 2014). Patients had 1) an index MM diagnosis on or after 1 January 2007, 2) medical prescription coverage in place at diagnosis, 3) no prior malignancies in the one‐year period prior to index diagnosis, 4) a one‐year look‐back period prior to index diagnosis, and 5) received ≥1 lines of therapy. Patients were considered transplant eligible if they received stem cell transplantation anytime during the follow‐up period. Baseline characteristics including comorbidities, index age, frontline treatment regimens and attrition rates at each subsequent line of therapy were characterized. Attrition was defined as the percentage of patients who did not have any recorded subsequent MM treatments as a result of death or lost to follow‐up in the database for any reason, including end of the database.Results:A total of 1,599 patients were included in this analysis. Baseline patient characteristics and pre‐existing comorbidities are summarized in Table 1. The induction regimens used as frontline treatments included bortezomib/dexamethasone (22%), lenalidomide/dexamethasone (13%), bortezomib/lenalidomide/dexamethasone (25%), all other bortezomib combinations (20%), and other (20%). The proportions of patients observed to progress to each subsequent line of therapy are summarized in Table 2. In total, 77% of patients received a second line of therapy, and only 55% received a third line treatment. The proportion of patients not receiving a subsequent line of therapy due to death is also summarized by lines of therapy in Table 2.Summary/Conclusion:A substantial number of patients with NDMM who are transplant eligible did not receive subsequent lines of therapy, with attrition by lines of therapy ranging from 23–40%. The increase in attrition rates with each additional line of therapy underscores the need to utilize upfront therapy associated with optimal progression‐free survival. Further studies evaluating the etiologic basis for this unexpectedly high attrition rate are warranted.image

Background The growth of the US cardiac transplant waiting list has outpaced the increase in donors, resulting in a widening gap between the number of waiting recipients and available donors. These trends have generated concern that longer waiting times may result in more patients deteriorating to urgent status and that transplanting only patients who are in an advanced state of decompensation will reduce posttransplant survival. Furthermore, the shortage of donors may result in extending the guidelines for donor acceptability to a degree that increases graft failure and posttransplant mortality. We measured these secular trends in the Cardiac Transplant Research Database to provide current data on time-dependent changes in US cardiac transplant practice and survival. Methods and Results At the time of this analysis, the Cardiac Transplant Research Database included all 2749 patients transplanted from January 1, 1990, to June 30, 1994, in the 25 participating transplant centers. During this 4.5-year period, the median waiting time for recipients who received a transplant increased from 2.7 to 3.5 months ( P <.0001), and the proportion of recipients whose status was urgent at transplantation increased from 41% to 60% ( P <.0001). Donor ischemic time increased from 150 to 166 minutes ( P <.0001), and the proportion of donors requiring pressor support increased from 68% to 85% ( P <.0001). Despite these changes in practice, the 1-year survival rate remained constant at 84% during this 4.5-year interval. There was no significant difference in 1-year survival rate between urgent status patients (83%) and nonurgent status patients (85%) ( P =.08). Conclusions The widening gap between the number of waiting recipients and the number of donors has resulted in a continuing trend toward transplanting urgent status recipients and to a liberalization of donor acceptance criteria. Despite these changes, posttransplant survival has remained constant.