Faculty Bibliography

Heart transplantation remains a critical therapy for patients with end-stage heart failure, offering incremental survival and improved quality of life. One of the key components behind the success of heart transplantation is the condition and preservation of the donor heart. In this review, we provide a comprehensive overview of ischemic reperfusion injury, risk factors associated with primary graft dysfunction, current use of various preservation solutions for organ procurement and recent advancements in donor heart procurement technologies. This State-of-the-Art review will explore factors associated with bringing the "ideal" donor heart to the operating room in the contemporary era.

BACKGROUND:Because of advances in medical treatment of heart failure, patients are living longer than in previous eras and may approach the need for advanced therapies, including heart transplantation, at older ages. This study assesses practices surrounding heart transplant in older adults (> 70 years) and examines short- and medium-term outcomes. METHODS AND RESULTS/RESULTS:This study is a retrospective analysis using the United Network for Organ Sharing (UNOS) database from 2010 to 2021. The absolute number of older adults being transplanted is increasing. Older adults were more likely to have had a prior malignancy or ischemic cardiomyopathy and less likely to be on extra-corporeal membrane oxygenation or have a high UNOS status prior to transplant. Mortality at 1-year was higher for older adults (27.8% vs. 23.4%), but at 5 years there was no significant difference (22.3% vs. 19.4%.). Older adults were more likely to die of malignancy or infection. Adults under 70 were more likely to die of cardiovascular causes or graft failure. There was less rejection in older adults. Mortality has not changed for older adults transplanted before versus after the 2018 UNOS allocation change. CONCLUSIONS:Carefully selected older adults may be considered for heart transplantation, given similar intermediate-term mortality.

BACKGROUND:Thoracoabdominal normothermic regional perfusion (TA-NRP) has emerged as a powerful technique for optimizing organ procurement from donation after circulatory death donors. Despite its rapid adoption, standardized guidelines for TA-NRP implementation are lacking, prompting the need for consensus recommendations to ensure safe and effective utilization of this technique. METHODS:A working group composed of members from The American Society of Transplant Surgeons, The International Society of Heart and Lung Transplantation, The Society of Thoracic Surgeons, and The American Association for Thoracic Surgery was convened to develop technical guidelines for TA-NRP. The group systematically reviewed existing literature, consensus statements, and expert opinions to identify key areas requiring standardization, including predonation evaluation, intraoperative management, postdonation procedures, and future research directions. RESULTS:The working group formulated recommendations encompassing donor evaluation and selection criteria, premortem testing and therapeutic interventions, communication protocols, and procedural guidelines for TA-NRP implementation. These recommendations aim to facilitate coordination among transplant teams, minimize variability in practice, and promote transparency and accountability throughout the TA-NRP process. CONCLUSIONS:The consensus guidelines presented herein serve as a comprehensive framework for the successful and ethical implementation of TA-NRP programs in organ procurement from donation after circulatory death donors. By providing standardized recommendations and addressing areas of uncertainty, these guidelines aim to enhance the quality, safety, and efficiency of TA-NRP procedures, ultimately contributing to improved outcomes for transplant recipients.

INTRODUCTION:Thoracoabdominal normothermic regional perfusion (TA-NRP) following cardiac death is an emerging multivisceral organ procurement technique. Recent national studies on outcomes of presumptive TA-NRP-procured organs are limited by potential misclassification since TA-NRP is not differentiated from donation after cardiac death (DCD) in registry data. METHODS:We studied 22 donors whose designees consented to TA-NRP and organ procurement performed at our institution between January 20, 2020 and July 3, 2022. We identified these donors in SRTR to describe organ utilization and recipient outcomes and compared them to recipients of traditional DCD (tDCD) and donation after brain death (DBD) organs during the same timeframe. RESULTS:All 22 donors progressed to cardiac arrest and underwent TA-NRP followed by heart, lung, kidney, and/or liver procurement. Median donor age was 41 years, 55% had anoxic brain injury, 45% were hypertensive, 0% were diabetic, and median kidney donor profile index was 40%. TA-NRP utilization was high across all organ types (88%-100%), with a higher percentage of kidneys procured via TA-NRP compared to tDCD (88% vs. 72%, p = .02). Recipient and graft survival ranged from 89% to 100% and were comparable to tDCD and DBD recipients (p ≥ .2). Delayed graft function was lower for kidneys procured from TA-NRP compared to tDCD donors (27% vs. 44%, p = .045). CONCLUSION:Procurement from TA-NRP donors yielded high organ utilization, with outcomes comparable to tDCD and DBD recipients across organ types. Further large-scale study of TA-NRP donors, facilitated by its capture in the national registry, will be critical to fully understand its impact as an organ procurement technique.

BACKGROUND:Thoracoabdominal normothermic regional perfusion (TA-NRP) has emerged as a powerful technique for optimizing organ procurement from donation after circulatory death donors. Despite its rapid adoption, standardized guidelines for TA-NRP implementation are lacking, prompting the need for consensus recommendations to ensure safe and effective utilization of this technique. METHODS:A working group composed of members from The American Society of Transplant Surgeons, The International Society of Heart and Lung Transplantation, The Society of Thoracic Surgeons, and The American Association for Thoracic Surgery was convened to develop technical guidelines for TA-NRP. The group systematically reviewed existing literature, consensus statements, and expert opinions to identify key areas requiring standardization, including predonation evaluation, intraoperative management, postdonation procedures, and future research directions. RESULTS:The working group formulated recommendations encompassing donor evaluation and selection criteria, premortem testing and therapeutic interventions, communication protocols, and procedural guidelines for TA-NRP implementation. These recommendations aim to facilitate coordination among transplant teams, minimize variability in practice, and promote transparency and accountability throughout the TA-NRP process. CONCLUSIONS:The consensus guidelines presented herein serve as a comprehensive framework for the successful and ethical implementation of TA-NRP programs in organ procurement from donation after circulatory death donors. By providing standardized recommendations and addressing areas of uncertainty, these guidelines aim to enhance the quality, safety, and efficiency of TA-NRP procedures, ultimately contributing to improved outcomes for transplant recipients.

Since the development of the first heart allocation system in 1988 to the most recent heart allocation system in 2018, the road to heart transplantation has continued to evolve. Policies were shaped with advances in temporary and durable left ventricular assist devices as well as prioritization of patients based on degree of illness. Herein, we review the changes in the heart allocation system over the past several decades and the impact of practice patterns across the United States.

In a previous study, heart xenografts from 10-gene-edited pigs transplanted into two human decedents did not show evidence of acute-onset cellular- or antibody-mediated rejection. Here, to better understand the detailed molecular landscape following xenotransplantation, we carried out bulk and single-cell transcriptomics, lipidomics, proteomics and metabolomics on blood samples obtained from the transplanted decedents every 6 h, as well as histological and transcriptomic tissue profiling. We observed substantial early immune responses in peripheral blood mononuclear cells and xenograft tissue obtained from decedent 1 (male), associated with downstream T cell and natural killer cell activity. Longitudinal analyses indicated the presence of ischemia reperfusion injury, exacerbated by inadequate immunosuppression of T cells, consistent with previous findings of perioperative cardiac xenograft dysfunction in pig-to-nonhuman primate studies. Moreover, at 42 h after transplantation, substantial alterations in cellular metabolism and liver-damage pathways occurred, correlating with profound organ-wide physiological dysfunction. By contrast, relatively minor changes in RNA, protein, lipid and metabolism profiles were observed in decedent 2 (female) as compared to decedent 1. Overall, these multi-omics analyses delineate distinct responses to cardiac xenotransplantation in the two human decedents and reveal new insights into early molecular and immune responses after xenotransplantation. These findings may aid in the development of targeted therapeutic approaches to limit ischemia reperfusion injury-related phenotypes and improve outcomes.

The physiologic impact of pulsatile flow (PF) on end-organ perfusion during cardiopulmonary bypass (CPB) is controversial. Using an intra-aortic balloon pump (IABP) to maintain PF during CPB for patients undergoing heart transplantation (HT) may impact end-organ perfusion, with implications for postoperative outcomes. A single-center retrospective study of 76 patients bridged to HT with IABP was conducted between January 2018 and December 2022. Beginning in May 2022, patients received IABP-generated PF during CPB at an internal rate of 80 beats/minute. Fifty-eight patients underwent HT with the IABP turned off (IABP-Off), whereas 18 patients underwent HT with IABP-generated PF (IABP-On). The unmatched IABP-On group experienced shorter organ ischemia times (180 vs. 203 minutes, p = 0.015) and CPB times (104 vs. 116 minutes, p = 0.022). The cohort was propensity matched according to age, organ ischemia time, and CPB time. Elevations in postoperative lactates in the immediate (2.8 vs. 1.5, p = 0.062) and 24 hour (4.7 vs. 2.4, p = 0.084) postoperative periods trended toward significance in the matched IABP-Off group. There was no difference in postoperative vasoactive inotropic score (VIS), postoperative creatinine, or length of stay. This limited preliminary data suggest that maintaining counterpulsation to generate PF during CPB may improve end-organ perfusion in this patient population as suggested by lower postoperative lactate levels.