Department of Cardiac Surgery, University Hospitals Leuven, Leuven, Belgium.
Cardiac Surgery Department, Pitié-Salpétrière Hospital, APHP, Sorbonne University, Paris, France.
Lancet. 2024 Aug 17;404(10453):670-682. doi: 10.1016/S0140-6736(24)01078-X.
Static cold storage (SCS) remains the gold standard for preserving donor hearts before transplantation but is associated with ischaemia, anaerobic metabolism, and organ injuries, leading to patient morbidity and mortality. We aimed to evaluate whether continuous, hypothermic oxygenated machine perfusion (HOPE) of the donor heart is safe and superior compared with SCS.
We performed a multinational, multicentre, randomised, controlled, open-label clinical trial with a superiority design at 15 transplant centres across eight European countries. Adult candidates for heart transplantation were eligible and randomly assigned in a 1:1 ratio. Donor inclusion criteria were age 18-70 years with no previous sternotomy and donation after brain death. In the treatment group, the preservation protocol involved the use of a portable machine perfusion system ensuring HOPE of the resting donor heart. The donor hearts in the control group underwent ischaemic SCS according to standard practices. The primary outcome was time to first event of a composite of either cardiac-related death, moderate or severe primary graft dysfunction (PGD) of the left ventricle, PGD of the right ventricle, acute cellular rejection at least grade 2R, or graft failure (with use of mechanical circulatory support or re-transplantation) within 30 days after transplantation. We included all patients who were randomly assigned, fulfilled inclusion and exclusion criteria, and received a transplant in the primary analysis and all patients who were randomly assigned and received a transplant in the safety analyses. This trial was registered with ClicalTrials.gov (NCT03991923) and is ongoing.
A total of 229 patients were enrolled between Nov 25, 2020, and May 19, 2023. The primary analysis population included 204 patients who received a transplant. There were no patients who received a transplant lost to follow-up. All 100 donor hearts preserved with HOPE were transplantable after perfusion. The primary endpoint was registered in 19 (19%) of 101 patients in the HOPE group and 31 (30%) of 103 patients in the SCS group, corresponding to a risk reduction of 44% (hazard ratio 0·56; 95% CI 0·32-0·99; log-rank test p=0·059). PGD was the primary outcome event in 11 (11%) patients in the HOPE group and 29 (28%) in the SCS group (risk ratio 0·39; 95% CI 0·20-0·73). In the HOPE group, 63 (65%) patients had a reported serious adverse event (158 events) versus 87 (70%; 222 events) in the SCS group. Major adverse cardiac transplant events were reported in 18 (18%) and 33 (32%) patients in the HOPE and SCS group (risk ratio 0·56; 95% CI 0·34-0·92).
Although there was not a significant difference in the primary endpoint, the 44% risk reduction associated with HOPE was suggested to be a clinically meaningful benefit. Post-transplant complications, measured as major adverse cardiac transplant events, were reduced. Analysis of secondary outcomes suggested that HOPE was beneficial in reducing primary graft dysfunction. HOPE in donor heart preservation addresses the existing challenges associated with graft preservation and the increasing complexity of donors and heart transplantation recipients. Future investigation will help to further elucidate the benefit of HOPE.
XVIVO Perfusion.
静态冷存储（SCS）仍然是移植前保存供体心脏的金标准，但与缺血、无氧代谢和器官损伤有关，导致患者发病率和死亡率增加。我们旨在评估供体心脏的连续低温充氧机器灌注（HOPE）是否安全且优于 SCS。
我们在 8 个欧洲国家的 15 个移植中心进行了一项多中心、多国、随机、对照、开放标签的临床试验，设计为优效性。符合条件的候选人为接受心脏移植的成年人，并按 1:1 的比例随机分配。供体纳入标准为年龄 18-70 岁，无先前开胸史和脑死亡后捐献。在治疗组中，保存方案涉及使用便携式机器灌注系统，以确保供体心脏的 HOPE。对照组中的供体心脏按照标准实践进行缺血 SCS。主要结局是移植后 30 天内发生心脏相关死亡、左心室中度或重度原发性移植物功能障碍（PGD）、右心室 PGD、至少 2R 级急性细胞排斥或移植物衰竭（使用机械循环支持或再次移植）的复合事件的时间。我们将所有随机分配、符合纳入和排除标准且接受移植的患者纳入主要分析，将所有随机分配且接受移植的患者纳入安全性分析。该试验在 ClicalTrials.gov（NCT03991923）注册，正在进行中。
2020 年 11 月 25 日至 2023 年 5 月 19 日期间共纳入 229 例患者。主要分析人群包括 204 例接受移植的患者。没有接受移植的患者失访。经灌注后，100 例 HOPE 保存的供体心脏全部可移植。HOPE 组 101 例患者中有 19 例（19%）和 SCS 组 103 例患者中有 31 例（30%）发生主要终点事件，风险降低 44%（风险比 0.56；95%CI 0.32-0.99；对数秩检验 p=0.059）。HOPE 组中有 11 例（11%）患者和 SCS 组中有 29 例（28%）患者发生原发性移植物功能障碍为主要结局事件（风险比 0.39；95%CI 0.20-0.73）。HOPE 组中 63 例（65%）患者发生了 158 次严重不良事件（AE），SCS 组中 87 例（70%）患者发生了 222 次严重不良事件。HOPE 组和 SCS 组分别有 18 例（18%）和 33 例（32%）患者发生主要不良心脏移植事件（风险比 0.56；95%CI 0.34-0.92）。
尽管主要终点没有显著差异，但 HOPE 相关的 44%风险降低提示具有临床意义的益处。移植后并发症，以主要不良心脏移植事件衡量，有所减少。次要结局分析表明，HOPE 有益于减少原发性移植物功能障碍。HOPE 在供体心脏保存中解决了与移植物保存相关的现有挑战以及供体和心脏移植受者日益增加的复杂性。未来的研究将有助于进一步阐明 HOPE 的益处。
XVIVO 灌注。
