Saint Luke's Mid America Heart Institute, Kansas City, MO; University of Missouri-Kansas City School of Medicine, Kansas City, MO.
University of Missouri-Kansas City School of Medicine, Kansas City, MO.
J Card Fail. 2024 Apr;30(4):613-617. doi: 10.1016/j.cardfail.2023.10.483. Epub 2023 Nov 21.
Inhibition of the mammalian target of rapamycin (mTor) pathway after heart transplantation has been associated with reduced progression of coronary allograft vasculopathy (CAV). The application of low-dose mTOR inhibition in the setting of modern immunosuppression, including tacrolimus, remains an area of limited exploration.
This retrospective study included patients who received heart transplantation between January 2009 and January 2019 and had baseline, 1-year and 2-3-year coronary angiography with intravascular ultrasound (IVUS). Intimal thickness in 5 segments along the left anterior descending artery was compared across imaging time points in patients who were transitioned to low-dose mTOR inhibitor (sirolimus) vs standard treatment with mycophenolate on a background of tacrolimus. Long-term adverse cardiovascular outcomes (revascularization, severe CAV, retransplant, and cardiovascular death) were also assessed.
Among 216 patients (mean age 51.5 ± 11.9 years, 77.8% men, 80.1% white), 81 individuals (37.5%) were switched to mTOR inhibition. mTOR inhibition was associated with a reduction in intimal thickness by 0.05 mm (95% CI 0.02-0.07; P < 0.001). This reduction was driven by patients who met the criteria for rapidly progressive CAV 1-year post-transplant (0.12 mm; P = 0.016 for interaction). After a median follow-up of 8.6 (IQR 6.6-11) years, 40 patients had major adverse cardiovascular outcomes. The use of mTOR inhibitors was not significantly associated with cardiovascular outcomes (P = 0.669).
Transitioning patients after heart transplantation to an immunosuppression regimen composed of low-dose mTOR inhibition and tacrolimus was associated with a lack of progression of CAV, particularly in those with rapidly progressive CAV at 1 year, but not with long-term cardiovascular outcomes.
在心脏移植后抑制哺乳动物雷帕霉素靶蛋白（mTor）途径与冠状动脉移植血管病（CAV）的进展减少有关。在包括他克莫司在内的现代免疫抑制背景下应用低剂量 mTor 抑制剂的情况仍处于探索有限的领域。
这项回顾性研究纳入了 2009 年 1 月至 2019 年 1 月期间接受心脏移植的患者，并进行了基线、1 年和 2-3 年的冠状动脉造影和血管内超声（IVUS）检查。在他克莫司背景下转换为低剂量 mTor 抑制剂（西罗莫司）与标准治疗（霉酚酸酯）的患者中，比较左前降支 5 个节段的内膜厚度在不同影像学时间点的变化。还评估了长期不良心血管结局（血运重建、严重 CAV、再次移植和心血管死亡）。
在 216 例患者（平均年龄 51.5 ± 11.9 岁，77.8%为男性，80.1%为白人）中，81 例（37.5%）患者转为 mTor 抑制剂治疗。mTor 抑制剂治疗与内膜厚度减少 0.05mm 相关（95%CI 0.02-0.07；P<0.001）。这种减少是由移植后 1 年迅速进展的 CAV 患者引起的（0.12mm；P=0.016 用于交互作用）。中位随访 8.6（IQR 6.6-11）年后，40 例患者发生主要不良心血管结局。mTor 抑制剂的使用与心血管结局无显著相关性（P=0.669）。
心脏移植后转换为包含低剂量 mTor 抑制剂和他克莫司的免疫抑制方案的患者，与 CAV 进展减少相关，特别是在移植后 1 年迅速进展的 CAV 患者中，但与长期心血管结局无关。
