Takeda, Koji

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.

Introduction: Sarcopenia, characterized by loss of muscle mass and function, is prevalent in heart failure (HF) and associated with poor outcomes. We investigated alterations in sarcopenia index (SI), a surrogate marker of skeletal muscle mass, in HF, left ventricular assist device (LVAD) and heart transplant (HT) and assessed its relationship with inflammation and digestive tract (gut and oral) microbiota. Hypothesis: Sarcopenia will be associated with increased inflammation, dysbiotic microbial signatures, higher HF class, and earlier time post-HT or post LVAD. Methods: We enrolled 460 HF, LVAD and HT patients. Repeated measures pre and post procedures were obtained in a subset of LVAD and HT patients. Sarcopenia index (serum Creatinine/Cystatin C) and inflammatory biomarkers (C-reactive protein, interleukin-6, tumor necrosis factor-alpha) were measured in 271 and 622 blood samples, respectively. Gut and saliva microbiota were assessed via 16S rRNA sequencing among 335 stool and 341 saliva samples. Multivariable regression models were used to assess the relationship between SI and i) New York Heart Association class; ii) pre- vs. post-LVAD or HT; iii) biomarkers of inflammation and microbial diversity. Results: Median (interquartile range) ln-SI was -0.13(-0.32,0.05). Ln-SI decreased across worsening HF class, further declined within the 1-month after LVAD and HT and rebounded over time to the levels of symptomatic HF. Ln-SI demonstrated an inverse correlation with inflammation (r=-0.28, p<0.0001), and a positive correlation with gut (r=0.26, p<0.0001) and oral microbial diversity (r=0.24, p<0.0001). Presence of the gut taxa Roseburia inulinivorans was associated with increased SI. Conclusions: SI levels decreased in symptomatic HF and remained decreased long-term after LVAD and HT. SI levels covaried with inflammation, gut and oral microbiota in a similar fashion.