Faculty Bibliography

As hepatitis C virus (HCV) infection is now curable, HCV-positive donor organs have expanded the deceased donor pool. Using OPTN data, we identified adult kidney, liver, heart, and lung candidates listed between 2016-2025 and evaluated rates of consent to accept HCV antibody-positive (Ab+) and HCV viremic (NAT+) organs. Temporal trends were described, and multilevel modified Poisson regression with center-level random effects was used to estimate adjusted risk ratios for candidate factors and quantify center variation using median incidence rate ratios (MIRR). Rates of consent to accept both HCV Ab+ and NAT+ organs rose over time. By the end of follow-up, consent rates for HCV Ab+ organs were 63.1% for kidney, 80.6% for liver, 73.3% for heart, and 72.1% for lung candidates, and consent rates for NAT+ organs were 44.9%, 70.7%, 50.5%, and 46.1%, respectively. Associations between candidate characteristics and consent were small after adjustment for center, whereas center effects were large. For HCV Ab+ organs, MIRRs were 6.31 (kidney), 2.48 (liver), 2.90 (heart), and 4.36 (lung); for NAT+ organs, MIRRs were even higher, 9.65, 3.19, 4.00, and 7.30, respectively, indicating marked between-center variability. Our analyses suggest that access to HCV-positive organs is influenced more by center practices than patient characteristics.

We aimed to investigate myocardial temperatures of allografts after removal from cold static storage (CSS) and the relationship between temperature and early outcomes of heart transplantation (HT). Between January and September 2024, 22 allografts preserved with CSS underwent prospective temperature measurements at the left ventricular free wall (LVFW) and interventricular septum; preservation solution temperatures were also measured. Median LVFW temperature was 4.0°C, septal temperature was 3.9°C, and solution temperature was 3.7°C. LVFW and septal temperatures were significantly correlated (p < 0.001), as were septal and solution temperatures (p = 0.03). Ischemic time inversely correlated with solution temperature (p = 0.021), and septal thickness correlated with septal temperature (p = 0.04). One patient developed severe primary graft dysfunction, and 30-day recipient and graft survival were 100% (22/22). We conclude that CSS maintains myocardial temperatures near 4°C, and it can achieve excellent post-HT outcomes with a low incidence of PGD.

OBJECTIVE:Post-cardiopulmonary bypass (post-CPB) vasoplegia syndrome (VS) is associated with a dysregulated inflammatory response and a higher morbidity and mortality, but the molecular pathways involved have been incompletely identified. We used multiplexed proteomic and transcriptomic analyses and targeted biochemical assays to identify the inflammatory and metabolic mediators that characterize post-CPB VS. METHODS:16 matched pairs of VS+ and VS- patients were analyzed pre-CPB and post-CPB for comparative proteomic and transcriptomic differences, with gene ontology (GO) pathway enrichment. Circulating NO metabolites (NOx), acetylcholine (ACh), and choline acetyltransferase (ChAT) levels were measured and correlated with VS. RESULTS:Baseline proteomic analysis demonstrated elevated TNF, IL-1R1 and IL-17RA in VS+ patients, with the activation of inflammatory cytokine, leukocyte activation, and NO biosynthesis pathways. Analysis of temporal pre-to-post-CPB proteomic changes in VS+ patients demonstrated post-CPB elevation IL17A, CXCL2, and VEGFR/FLT, and decreased immune resolving proteins. Post-CPB proteomic analysis demonstrated differential activation of leukocyte trafficking, T-cell differentiation, IL-6, and IL-17 pathways in VS+ patients. Transcriptomic analysis demonstrated post-CPB activation of cellular response to hypoxia, cellular stress response, and decreased response to angiotensin pathways. Circulating NOx, ACh, and ChAT levels were elevated pre-CPB in VS+ patients and increased further post-CPB. Pre-CPB ACh had a 99% AUC correlation with post-CPB VS+. CONCLUSIONS:We demonstrated increased baseline cardiovascular inflammation in VS+ patients, which predisposed them to a dysregulated response to CPB, and we identified CPB-induced activation of IL-17 skewed multi-cytokine inflammatory pathways and endothelial activation as mechanistic mediators of post-CPB VS. Circulating ACh was identified as a potential biomarker.

BACKGROUND:Donation after the circulatory determination of death (DCD) heart transplantation (HT) is becoming more widely adopted across the United States (US) and Europe. OBJECTIVE:This study compared donor and recipient demographics, intraoperative parameters, and outcomes between DCD HT centers in Europe and the US that contributed to the Outcomes after DCD Cardiac Transplantation Database. METHODS:This was a retrospective observational study across 22 HT centers in Belgium, Spain, the United Kingdom (UK), and the US. All patients undergoing DCD HT at participating centers, from the start of each center's DCD program through 01/01/2023, were included with censor date 01/01/2024. The primary outcome was 1-year survival. Secondary outcomes included severe primary graft dysfunction and incidence of acute cellular rejection. RESULTS:Data from 223 patients in Europe and 281 in the US were analyzed. DCD donors in Europe were significantly older (37 years vs 28 years; p < 0.001). Recipients in Europe had inferior 1-year survival (86.6% vs 91.8%; p = 0.043), but 1-month and 3-years survival were similar. 1-year survival in the direct procurement and preservation (DPP) cohort was significantly higher in the US group (91.2% vs 82.6%; p = 0.02). In the thoraco-abdominal normothermic regional perfusion (taNRP) cohort 1-year survival was similar between Europe and the US. Recipients in Europe had higher use of mechanical circulatory assist post-transplant (17.9% vs 11%; p = 0.03). CONCLUSION/CONCLUSIONS:This study further confirms the safety and efficacy of DCD HT across centers in the US and Europe, despite important differences in donor and recipient demographics and clinical outcomes. Continued collection of international data may identify opportunities to improve outcomes.

The inaugural Richard Slayman Clinical Xenotransplantation Workshop convened >140 participants from North America, Europe, and Asia to discuss emerging advances and challenges in translating xenotransplantation from bench to bedside. This report summarized key discussions spanning kidney, heart, and liver xenotransplantation, with an emphasis on clinical readiness and future directions. Core themes included the importance of patient selection, the role of genetic editing to reduce immune incompatibility, adaptive immunosuppressive strategies, novel molecular tools for immune and infectious surveillance, and the growing recognition of innate immune activation as a barrier to long-term graft survival. The workshop highlighted decedent models as a translational bridge, the use of machine perfusion in liver xenograft applications, and progress in living recipients. Notably, 1 patient achieved 9 mo of kidney xenograft function, underscoring the feasibility of extended survival in carefully selected candidates. Perspectives from patients and families, including a reflection honoring Richard Slayman, the first living recipient of a genetically edited pig kidney, framed the scientific dialogue within the broader human impact of this emerging field. The workshop marked a pivotal moment in aligning scientific, ethical, and regulatory efforts to advance safe and equitable access to xenotransplantation.

BACKGROUND:Multiorgan heart and kidney transplants (HKTx) performed for patients with end-stage heart failure and chronic kidney disease have increased in recent years. However, no established protocols exist on whether a heart and kidney from the same donor should be transplanted in the same operation versus 1-2 days apart. METHODS:Using SRTR data 1993-2023, we compared same-donor HKTx recipients with both transplants performed on the same day ("simultaneous") to recipients with kidney transplants performed within 1 day of the heart transplant ("staged"). We examined differences in weighted post-transplant clinical characteristics using average treatment effect. Post-transplant mortality and graft failure was also assessed using Kaplan-Meier curves and instrumental variable analysis adjusted for recipient characteristics and year of transplant. RESULTS:, p < 0.001). Weighted patient mortality, all cause heart failure (ACHF), and all cause kidney failure (ACKF) 4 years post-transplant were slightly lower for simultaneous versus staged HKTx recipients (17.1% vs. 19.9%, 17.2% vs. 20.1%, 20.8% vs. 24.7%). However, instrumental variable analysis found no meaningful differences in adjusted patient survival, ACHF, or ACKF by HKTx type. CONCLUSION/CONCLUSIONS:Simultaneous HKTx recipients have shorter hospital stays, decreased mortality, and higher rates of graft survival post-transplant compared to staged HKTx recipients, which may reflect favorable patient factors that enable both operations to be performed on the same day rather than an inherent benefit of simultaneous HKTx, given equivalent adjusted patient mortality, ACHF, and ACKF.

BACKGROUND:Heart utilization from donation after circulatory death (DCD) donors remains highly variable across the United States, potentially resulting in missed transplantation opportunities. This study aimed to quantify the frequency of clinically viable, non-utilized DCD hearts and identify usage barriers. METHODS:We conducted a retrospective, national registry analysis of donors ≤55 years old who donated ≥1 organ, focusing primarily on DCDs. Donor characteristics, particularly age, warm ischemic time (WIT), and EF, as well as reasons for non-recovery and offer refusal, were analyzed. SRTR's heart yield model was employed to identify non-utilized DCD hearts clinically comparable to transplanted DCD hearts. RESULTS:In 2023, 613 DCD hearts were transplanted, accounting for 13.5% of all heart transplants. Only 15.5% of DCD hearts from donors ≤55 years old were utilized. Marked variation in risk-adjusted DCD heart yield was observed between states, OPOs, and Regions. Donors of transplanted DCD hearts had a median age of 32, WIT 24 minutes, and EF 63%. The yield model identified between 701-1,243 non-utilized DCD hearts with characteristics comparable to transplanted cases. Concerns about delayed progression to circulatory arrest after life support withdrawal was a key reason for non-utilization. CONCLUSIONS:Despite wider acceptance of DCD heart transplantation, an increasing proportion of DCD hearts remain unused despite favorable characteristics. Concerns related to delayed progression to circulatory arrest are a significant barrier to heart utilization. Addressing geographic variability and improving predictive models for donor viability could double DCD heart utilization and expand heart transplantation volume by approximately 700-1,200 (15-27%) annually.

BACKGROUND:Despite the goal of the 2018 revision to the heart allocation policy to reduce reliance on exception requests through improved granularity in status criteria, there has been a dramatic rise in exception requests. OBJECTIVES/OBJECTIVE:This study evaluated trends in exception use over the first 6 years of the updated policy, assessing associated clinical factors, temporal changes, and impact on waitlist outcomes. METHODS:This retrospective transplant registry analysis included all adult isolated heart transplant candidates from October 18, 2018, to September 30, 2024. Candidates were stratified by exception use, listing era, and region. Exception use was compared using Wilcoxon rank-sum and chi-squared tests, with multilevel logistic regression assessing independent associations. Trends over time and across UNOS (United Network for Organ Sharing) regions were evaluated, and a competing risks framework examined time to transplant and waitlist mortality. RESULTS:Among 26,330 candidates, 38.6% used exception requests, with a statistically significant increase over time, particularly in higher priority statuses. Exception use was more common among Black, non-Hispanic candidates, and candidates with blood type O, and less likely for patients with blood type A (P < 0.001). Additionally, pretransplant isolated durable left ventricular assist devices were less common in candidates who requested exceptions (19.0% vs 31.6%; P < 0.001). Overall, 39.9% of exception candidates were listed at status 1 or 2 compared to 29% of nonexception candidates, and 69.2% of exception candidates were removed from the waitlist at status 1 or 2 compared with 37% of nonexception candidates. CONCLUSIONS:The rising use of exceptions underscores ongoing limitations in allocation criteria, and disparities suggesting inequities in access to higher listing status. Policy refinements are needed to ensure a balance between medical urgency and equitable allocation.