Inglis Sara S, Abbas Mohsin, Asleh Rabea, Garmany Armin, Smith Byron H, Kushwaha Sudhir, Pereira Naveen, Clavell Alfredo L, Villavicencio Mauricio A, Spencer Philip J, Daly Richard C, Behfar Atta, Rosenbaum Andrew N
Van Cleve Cardiac Regenerative Medicine Program, Mayo Clinic, Rochester, Minnesota; Deparment of Cardiovascular Medicine, Mayo Clinic, Rochester, Minnesota.
Deparment of Cardiovascular Medicine, Mayo Clinic, Rochester, Minnesota.
J Heart Lung Transplant. 2025 Jun;44(6):975-983. doi: 10.1016/j.healun.2024.12.014. Epub 2024 Dec 30.
Although recommended in International Society for Heart and Lung Transplantation (ISHLT) guidelines, transition to mammalian targets of rapamycin (mTOR) inhibitors in heart transplant recipients is not routinely performed, in part due to perceived risk of rejection. This study sought to evaluate the incidence and risk factors for biopsy-proven, clinically relevant rejection following conversion from calcineurin inhibitor (CNI) to sirolimus (SRL) immunosuppression.
A single center retrospective study was conducted of all consecutive adult patients who underwent orthotopic heart transplantation (OHT) and CNI-free SRL conversion from January 1999 to January 2023. All post-OHT biopsy data were obtained and graded per ISHLT criteria (antibody-mediated rejection [pAMR] or acute cellular rejection [ACR]). The primary endpoint was early rejection, defined as grade 2R ACR, pAMR 1, or greater, within 6 months after conversion.
Three hundred and seventeen patients (72% male, mean age 51.5±12.6 years) were included. Median time to SRL conversion following OHT was 0.76 years (IQR 0.49, 1.42). Median time from conversion to rejection was 0.51 years (IQR 0.31, 1.05). Thirty eight patients (12%) experienced early rejection. Following multivariate analysis, both timing to SRL conversion following OHT (OR 0.94 per month, 95% CI: 0.89-0.99, p-value=0.0054) and age at transplantation (OR 0.96, 95% CI: 0.93-0.99, p-value=0.0071) were independently associated with early rejection. Rejection following SRL conversion was not associated with increased risk of cardiac allograft vasculopathy (CAV) grade 2-3.
In a CNI-free SRL conversion protocol, both earlier SRL conversion following OHT and younger age at transplant are independently associated with early rejection, but rejection is not associated with a net increased risk of prognostically important CAV. Individualization of transition is necessary to mitigate risk, and these findings may aid in improvement of future conversion protocols.
尽管国际心肺移植协会（ISHLT）指南中有相关推荐，但心脏移植受者向雷帕霉素哺乳动物靶点（mTOR）抑制剂的转换并非常规进行，部分原因是认为存在排斥风险。本研究旨在评估从钙调神经磷酸酶抑制剂（CNI）转换为西罗莫司（SRL）免疫抑制后，经活检证实的临床相关排斥反应的发生率及危险因素。
对1999年1月至2023年1月期间所有接受原位心脏移植（OHT）并转换为无CNI的SRL免疫抑制的连续成年患者进行单中心回顾性研究。获取所有OHT后的活检数据，并根据ISHLT标准（抗体介导的排斥反应[pAMR]或急性细胞排斥反应[ACR]）进行分级。主要终点是早期排斥反应，定义为转换后6个月内2R级ACR、pAMR 1级或更高。
共纳入317例患者（72%为男性，平均年龄51.5±12.6岁）。OHT后转换为SRL的中位时间为0.76年（四分位间距0.49，1.42）。从转换到排斥反应的中位时间为0.51年（四分位间距0.31，1.05）。38例患者（12%）发生早期排斥反应。多因素分析后，OHT后转换为SRL的时间（每月OR 0.94，95%置信区间：0.89 - 0.99，p值 = 0.0054）和移植时年龄（OR 0.96，95%置信区间：0.93 - 0.99，p值 = 0.0071）均与早期排斥反应独立相关。SRL转换后的排斥反应与心脏移植血管病变（CAV）2 - 3级风险增加无关。
在无CNI的SRL转换方案中，OHT后更早的SRL转换和移植时更年轻的年龄均与早期排斥反应独立相关，但排斥反应与具有预后重要性的CAV净风险增加无关。转换的个体化对于降低风险是必要的，这些发现可能有助于改进未来的转换方案。
