Abstract：
The prognosis after heart transplantation continues to improve. Therefore, the prevention of chronic post-transplant sequelae, such as chronic kidney disease, allograft vasculopathy, and malignancies is becoming increasingly important. Everolimus, an inhibitor of the mammalian target of rapamycin (mTOR), is increasingly used for immunosuppression after heart transplantation. However, everolimus may cause a characteristic complex of adverse effects, including dyslipidemia. Currently there are no guidelines for the long-term screening and treatment of dyslipidemia in heart transplant recipients treated with everolimus. This article presents a clinical case of hypercholesterolemia that developed after the start of the everolimus treatment in a heart recipient. The patient was a 39-year-old man who underwent orthotopic heart transplantation for ischemic cardiomyopathy in 2012 (at the age of 27). In 2019, the patient\'s immunosuppressive therapy was converted from mycophenolate mofetil to everolimus due to the development of cardiac allograft vasculopathy. The change in the immunosuppressive therapy was associated with increases in total cholesterol and low-density lipoprotein cholesterol, which were not reversed with a combined lipid-lowering therapy (maximum doses of rosuvastatin, ezetimibe, fenofibrate). A decrease in lipid levels was achieved with a blocker of hepatic proprotein convertase subtilisin/kexin type 9 synthesis at the level of microribonucleic acid (inclisiran). This case demonstrates the difficulties in correcting dyslipidemia in patients with cardiac allograft, since the treatment with the immunosuppressant everolimus worsens existing dyslipidemia. However, the combination lipid-lowering therapy, that affects various elements of the pathogenesis (specifically, the combined inhibition of hydroxymethylglutaryl-CoA reductase with a statin, cholesterol absorption from the small intestine with ezetimibe, and PCSK9 messenger RNA with inclisiran), provides an effective control of blood lipids and minimizing the adverse effects of immunosuppressive therapy, such as cardiac allograft vasculopathy.
摘要：
心脏移植后预后持续改善。因此,预防慢性移植后后遗症，比如慢性肾病，同种异体血管病变，恶性肿瘤变得越来越重要。依维莫司,哺乳动物雷帕霉素靶蛋白（mTOR）的抑制剂，越来越多地用于心脏移植后的免疫抑制。然而,依维莫司可能会导致不良作用的特征性复杂，包括血脂异常.目前，尚无长期筛查和治疗依维莫司治疗的心脏移植受者血脂异常的指南。本文介绍了心脏接受者在依维莫司治疗开始后出现的高胆固醇血症的临床病例。患者是一名39岁的男性，2012年因缺血性心肌病接受了原位心脏移植（27岁）。2019年，由于心脏同种异体血管病变的发展，患者的免疫抑制治疗从霉酚酸酯转换为依维莫司。免疫抑制治疗的改变与总胆固醇和低密度脂蛋白胆固醇的增加有关，联合降脂治疗没有逆转（最大剂量的瑞舒伐他汀，ezetimibe,非诺贝特）。在微核糖核酸（inclisiran）水平上使用肝前蛋白转化酶枯草杆菌蛋白酶/kexin9型合成阻断剂实现了脂质水平的降低。该病例证明了心脏移植患者在纠正血脂异常方面的困难。因为用免疫抑制剂依维莫司治疗会使现有的血脂异常恶化。然而,联合降脂治疗，影响发病机理的各种因素(特别是，羟甲基戊二酰辅酶A还原酶与他汀类药物的联合抑制作用，用依泽替米贝从小肠吸收胆固醇，和具有inclisiran的PCSK9信使RNA），提供了有效的控制血脂和最大限度地减少免疫抑制治疗的不利影响，如心脏移植血管病变。
