[A Case of Successful Treatment of Severe Hyperlipidemia After Heart Transplantation With Inclisiran].

IF 0.5 4区 医学 Q4 CARDIAC & CARDIOVASCULAR SYSTEMS Kardiologiya Pub Date : 2024-07-31 DOI:10.18087/cardio.2024.7.n2679
Z G Tatarintseva, L K Tkhatl, K O Barbuhatti, E D Kosmacheva
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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.

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[英克利西兰成功治疗心脏移植术后严重高脂血症病例]。
心脏移植后的预后不断改善。因此,预防移植后慢性后遗症(如慢性肾病、异体移植血管病变和恶性肿瘤)变得越来越重要。依维莫司是哺乳动物雷帕霉素靶点(mTOR)的抑制剂,越来越多地被用于心脏移植后的免疫抑制。然而,依维莫司可能会引起一系列特有的不良反应,包括血脂异常。目前还没有关于接受依维莫司治疗的心脏移植受者血脂异常的长期筛查和治疗指南。本文介绍了一例心脏受者在开始接受依维莫司治疗后出现高胆固醇血症的临床病例。患者是一名 39 岁的男性,2012 年(27 岁)因缺血性心肌病接受了正位心脏移植手术。2019年,由于出现心脏同种异体移植血管病变,患者的免疫抑制疗法从霉酚酸酯(mycophenolate mofetil)改为依维莫司(everolimus)。免疫抑制疗法的改变导致总胆固醇和低密度脂蛋白胆固醇升高,而联合降脂疗法(最大剂量的洛伐他汀、依折麦布和非诺贝特)无法逆转这种情况。通过在微核糖核酸水平上阻断肝脏 9 型枯草蛋白酶/kexin 的合成(clinisiran),血脂水平有所下降。该病例表明,纠正心脏同种异体移植患者的血脂异常非常困难,因为使用免疫抑制剂依维莫司治疗会加重现有的血脂异常。然而,联合降脂疗法可影响发病机制的各种因素(特别是他汀类药物对羟甲基戊二酰-CoA 还原酶的联合抑制作用、依折麦布对小肠胆固醇吸收的抑制作用以及 inclisiran 对 PCSK9 信使 RNA 的抑制作用),从而有效控制血脂,并将免疫抑制疗法的不良反应(如心脏同种异体移植血管病变)降至最低。
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来源期刊
Kardiologiya
Kardiologiya 医学-心血管系统
CiteScore
1.70
自引率
20.00%
发文量
94
审稿时长
3-8 weeks
期刊介绍: “Kardiologiya” (Cardiology) is a monthly scientific, peer-reviewed journal committed to both basic cardiovascular medicine and practical aspects of cardiology. As the leader in its field, “Kardiologiya” provides original coverage of recent progress in cardiovascular medicine. We publish state-of-the-art articles integrating clinical and research activities in the fields of basic cardiovascular science and clinical cardiology, with a focus on emerging issues in cardiovascular disease. Our target audience spans a diversity of health care professionals and medical researchers working in cardiovascular medicine and related fields. The principal language of the Journal is Russian, an additional language – English (title, authors’ information, abstract, keywords). “Kardiologiya” is a peer-reviewed scientific journal. All articles are reviewed by scientists, who gained high international prestige in cardiovascular science and clinical cardiology. The Journal is currently cited and indexed in major Abstracting & Indexing databases: Web of Science, Medline and Scopus. The Journal''s primary objectives Contribute to raising the professional level of medical researchers, physicians and academic teachers. Present the results of current research and clinical observations, explore the effectiveness of drug and non-drug treatments of heart disease, inform about new diagnostic techniques; discuss current trends and new advancements in clinical cardiology, contribute to continuing medical education, inform readers about results of Russian and international scientific forums; Further improve the general quality of reviewing and editing of manuscripts submitted for publication; Provide the widest possible dissemination of the published articles, among the global scientific community; Extend distribution and indexing of scientific publications in major Abstracting & Indexing databases.
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