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<article article-type="research-article" dtd-version="1.3" xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" xml:lang="en"><front><journal-meta><journal-id journal-id-type="publisher-id">rpcardio</journal-id><journal-title-group><journal-title xml:lang="en">Rational Pharmacotherapy in Cardiology</journal-title><trans-title-group xml:lang="ru"><trans-title>Рациональная Фармакотерапия в Кардиологии</trans-title></trans-title-group></journal-title-group><issn pub-type="ppub">1819-6446</issn><issn pub-type="epub">2225-3653</issn><publisher><publisher-name>«SILICEA-POLIGRAF» LLC</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="doi">10.20996/1819-6446-2024-3022</article-id><article-id custom-type="edn" pub-id-type="custom">JNMVKN</article-id><article-id custom-type="elpub" pub-id-type="custom">rpcardio-3022</article-id><article-categories><subj-group subj-group-type="heading"><subject>Research Article</subject></subj-group><subj-group subj-group-type="section-heading" xml:lang="en"><subject>CURRENT QUESTIONS OF CLINICAL PHARMACOLOGY</subject></subj-group><subj-group subj-group-type="section-heading" xml:lang="ru"><subject>АКТУАЛЬНЫЕ  ВОПРОСЫ  КЛИНИЧЕСКОЙ ФАРМАКОЛОГИИ</subject></subj-group></article-categories><title-group><article-title>Cardiotoxicity mechanisms of antitumor therapy with immune checkpoint inhibitors: new achievements</article-title><trans-title-group xml:lang="ru"><trans-title>Механизмы кардиотоксичности противоопухолевой терапии ингибиторами иммунных контрольных точек: современные достижения</trans-title></trans-title-group></title-group><contrib-group><contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0002-1250-8798</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Хидирова</surname><given-names>Л. Д.</given-names></name><name name-style="western" xml:lang="en"><surname>Khidirova</surname><given-names>L. D.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Хидирова Людмила Даудовна</p><p>Новосибирск</p></bio><bio xml:lang="en"><p>Lyudmila D. Khidirova</p><p>Novosibirsk</p></bio><email xlink:type="simple">h_ludmila73@mail.ru</email><xref ref-type="aff" rid="aff-1"/></contrib><contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid">https://orcid.org/0009-0008-9078-5134</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Лацвиева</surname><given-names>А. Е.</given-names></name><name name-style="western" xml:lang="en"><surname>Latsvieva</surname><given-names>A. E.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Лацвиева Анастасия Евгеньевна</p><p>Новосибирск</p></bio><bio xml:lang="en"><p>Anastasia E. Latsvieva</p><p>Novosibirsk</p></bio><xref ref-type="aff" rid="aff-2"/></contrib><contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid">https://orcid.org/0009-0002-8340-9268</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Ведерин</surname><given-names>А. А.</given-names></name><name name-style="western" xml:lang="en"><surname>Vederin</surname><given-names>A. V.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Ведерин Александр Алексеевич</p><p>Новосибирск</p></bio><bio xml:lang="en"><p>Alexander V. Vederin</p><p>Novosibirsk</p></bio><xref ref-type="aff" rid="aff-2"/></contrib></contrib-group><aff-alternatives id="aff-1"><aff xml:lang="ru"><institution>Новосибирский государственный медицинский университет; Новосибирский областной клинический кардиологический диспансер</institution><country>Россия</country></aff><aff xml:lang="en"><institution>Novosibirsk State Medical University; Novosibirsk Regional Clinical Cardiology Dispensary</institution><country>Russian Federation</country></aff></aff-alternatives><aff-alternatives id="aff-2"><aff xml:lang="ru"><institution>Новосибирский государственный медицинский университет</institution><country>Russian Federation</country></aff><aff xml:lang="en"><institution>Novosibirsk State Medical University</institution><country>Russian Federation</country></aff></aff-alternatives><pub-date pub-type="collection"><year>2024</year></pub-date><pub-date pub-type="epub"><day>24</day><month>05</month><year>2024</year></pub-date><volume>20</volume><issue>2</issue><fpage>265</fpage><lpage>274</lpage><permissions><copyright-statement>Copyright &amp;#x00A9; Khidirova L.D., Latsvieva A.E., Vederin A.V., 2024</copyright-statement><copyright-year>2024</copyright-year><copyright-holder xml:lang="ru">Хидирова Л.Д., Лацвиева А.Е., Ведерин А.А.</copyright-holder><copyright-holder xml:lang="en">Khidirova L.D., Latsvieva A.E., Vederin A.V.</copyright-holder><license xml:lang="ru" license-type="creative-commons-attribution" xlink:href="https://creativecommons.org/licenses/by/4.0/" xlink:type="simple"><license-p>Данная работа распространяется под лицензией Creative Commons Attribution 4.0.</license-p></license><license xml:lang="en" license-type="creative-commons-attribution" xlink:href="https://creativecommons.org/licenses/by/4.0/" xlink:type="simple"><license-p>This work is licensed under a Creative Commons Attribution 4.0 License.</license-p></license></permissions><self-uri xlink:href="https://www.rpcardio.online/jour/article/view/3022">https://www.rpcardio.online/jour/article/view/3022</self-uri><abstract><p>The immune checkpoint inhibitors (ICTs) emergence has opened up new perspectives in cancer immunotherapy. Nevertheless, serious, including life-threatening conditions caused by ICT cardiotoxic effects pose a number of obstacles to clinical specialists. The lack of knowledge about pathophysiology of cardiovascular adverse events in the treatment of ICT tumors is one of the reasons why oncological specialists seek help from cardiologists. Some works consider the mechanisms of individual complications development, but the number of works that would systematize and summarize descriptions of all the most significant ICT inhibitor therapy complications is small. In this regard, a literature review on the use of ICT inhibitors was conducted with a search in PubMed, Embase, Web of Science, e-L ibrary, Google Scholar. The purpose was to analyze the accumulated data on the mechanisms of ICT therapy complications development; Preference was given to systematic reviews, randomized clinical trials, which would be supplemented by separate cohort studies and descriptions of some experiments. Thus, it was determined that the ICT inhibitors cardiotoxicity can affect any part of the cardiovascular system, causing changes in both inflammatory and non-inflammatory etiology. Understanding their mechanisms increases the ability of specialists to form an effective treatment strategy while minimizing the risk of complications. Although a lot of theoretical, experimental and clinical empirical data on the side effects of this class of anticancer drugs have been accumulated in oncological practice, the ICT inhibitors cardiotoxicity is a problem requiring further research.</p></abstract><trans-abstract xml:lang="ru"><p>Появление ингибиторов иммунных контрольных точек (ИКТ) открыло новые перспективы в иммунотерапии рака. Тем не менее, серьезные, в том числе опасные для жизни состояния, вызванные кардиотоксическими эффектами ИКТ, ставят перед клиническими специалистами ряд препятствий. Нехватка знаний об аспектах патофизиологии кардиоваскулярных нежелательных явлений терапии опухолей ИКТ является одной из причин обращения специалистов онкологического профиля за помощью к кардиологам. В РФ данная проблема является еще более актуальной в связи с тем, что в научной литературе не имеется первичных исследований, которые были бы посвящены детальному разбору вопросов патогенеза кардиоваскулярных нарушений, возникающих в ходе терапии ингибиторами ИКТ. В зарубежной литературе представлены работы, которые рассматривают механизмы развития отдельных осложнений, но число работ, которые бы систематизировали и суммировали описания всех наиболее значимых осложнений терапии ингибиторами ИКТ, невелико. В связи с этим был проведен обзор литературы по применению ингибиторов ИКТ с поиском в библиографических базах данных PubMed, Embase, Web of Scienсe, e- Library, Google Scholar, целью которого стал анализ накопленных данных о механизмах развития осложнений терапии ингибиторами ИКТ; предпочтение отдавалось систематическим обзорам, рандомизированным клиническим исследованиям, которые были бы дополнены отдельными когортными исследованиями и описанием некоторых экспериментов. Таким образом, определено, что кардиотоксичность ингибиторов ИКТ может затрагивать любой отдел сердечно-с осудистой системы, вызывая изменения как воспалительной (миокардит, перикардит, коронарный васкулит), так и невоспалительной этиологии (аритмии, невоспалительная дисфункция левого желудочка, такоцубоподобный синдром, коронарный вазоспазм и инфаркт миокарда на фоне атеросклероза). За счет разнообразия клинических проявлений, при относительной редкости, кардиотоксические реакции ингибиторов ИКТ могут создавать трудности при дифференциальной диагностике и лечении пациентов. Понимание же их механизмов повышает возможности специалистов в отношении формирования эффективной стратегии лечения с минимизацией риска осложнений. И хотя в онкологической практике накоплено немало теоретических, экспериментальных и клинико-э мпирических данных о побочных эффектах этого класса противоопухолевых препаратов, кардиотоксичность ингибиторов ИКТ представляет собой проблему, требующую дальнейших исследований.</p></trans-abstract><kwd-group xml:lang="ru"><kwd>кардиотоксичность</kwd><kwd>ингибиторы иммунных контрольных точек</kwd><kwd>иммуноопосредованные нежелательные реакции</kwd><kwd>миокардит</kwd><kwd>острый коронарный синдром</kwd><kwd>перикардит</kwd><kwd>дилатационная кардиомиопатия</kwd><kwd>синдром Такоцубо</kwd><kwd>аритмии.</kwd></kwd-group><kwd-group xml:lang="en"><kwd>cardiotoxicity</kwd><kwd>immune checkpoint inhibitors</kwd><kwd>immune-related adverse events</kwd><kwd>myocarditis</kwd><kwd>acute coronary syndrome</kwd><kwd>pericarditis</kwd><kwd>dilated cardiomyopathy</kwd><kwd>Takotsubo syndrome</kwd><kwd>arrhythmias</kwd></kwd-group></article-meta></front><back><ref-list><title>References</title><ref id="cit1"><label>1</label><citation-alternatives><mixed-citation xml:lang="ru">ESC Guidelines on cardio-oncology developed in collaboration with the European Hematology Association (EHA), the European Society for Therapeutic Radiology and Oncology (ESTRO) and the International Cardio-Oncology Society (IC-OS). Eur Heart J. 2022; 43(41):4229-4361. DOI:10.1093/eurheartj/ehac244.</mixed-citation><mixed-citation xml:lang="en">2022 ESC Guidelines on cardio-oncology developed in collaboration with the European Hematology Association (EHA), the European Society for Therapeutic Radiology and Oncology (ESTRO) and the International Cardio-Oncology Society (IC-OS). Eur Heart J. 2022; 43(41):4229-4361. DOI:10.1093/eurheartj/ehac244.</mixed-citation></citation-alternatives></ref><ref id="cit2"><label>2</label><citation-alternatives><mixed-citation xml:lang="ru">Hu J, Tian R, Ma Y, et al. Risk of cardiac adverse events in patients treated with immune checkpoint inhibitor regimens: a systematic review and metaanalysis. Front Oncol. 2021;11:645245. DOI:10.3389/fonc.2021.645245.</mixed-citation><mixed-citation xml:lang="en">Hu J, Tian R, Ma Y, et al. Risk of cardiac adverse events in patients treated with immune checkpoint inhibitor regimens: a systematic review and metaanalysis. Front Oncol. 2021;11:645245. DOI:10.3389/fonc.2021.645245.</mixed-citation></citation-alternatives></ref><ref id="cit3"><label>3</label><citation-alternatives><mixed-citation xml:lang="ru">Chhabra N, Kennedy J. A review of cancer immunotherapy toxicity: immune checkpoint inhibitors. J Med Toxicol. 2021;17(4):411-424. DOI:10.1007/s13181021-00833-8.</mixed-citation><mixed-citation xml:lang="en">Chhabra N, Kennedy J. A review of cancer immunotherapy toxicity: immune checkpoint inhibitors. J Med Toxicol. 2021;17(4):411-424. DOI:10.1007/s13181021-00833-8.</mixed-citation></citation-alternatives></ref><ref id="cit4"><label>4</label><citation-alternatives><mixed-citation xml:lang="ru">Tan S, Day D, Nicholls SJ, Segelov E. Immune checkpoint inhibitor therapy in oncology: current uses and future directions: JACC: CardioOncology state-of-the-art review. JACC CardioOncol. 2022;4(5):579-597. DOI:10.1016/j.jaccao.2022.09.004.</mixed-citation><mixed-citation xml:lang="en">Tan S, Day D, Nicholls SJ, Segelov E. Immune checkpoint inhibitor therapy in oncology: current uses and future directions: JACC: CardioOncology state-of-the-art review. JACC CardioOncol. 2022;4(5):579-597. DOI:10.1016/j.jaccao.2022.09.004.</mixed-citation></citation-alternatives></ref><ref id="cit5"><label>5</label><citation-alternatives><mixed-citation xml:lang="ru">Franzin R, Netti GS, Spadaccino F, et al. The use of immune checkpoint inhibitors in oncology and the occurrence of AKI: where do we stand? Front Immunol. 2020;11:574271. DOI:10.3389/fimmu.2020.574271.</mixed-citation><mixed-citation xml:lang="en">Franzin R, Netti GS, Spadaccino F, et al. The use of immune checkpoint inhibitors in oncology and the occurrence of AKI: where do we stand? Front Immunol. 2020;11:574271. DOI:10.3389/fimmu.2020.574271.</mixed-citation></citation-alternatives></ref><ref id="cit6"><label>6</label><citation-alternatives><mixed-citation xml:lang="ru">Chocarro L, Blanco E, Zuazo M, et al. Understanding LAG-3 signaling. Int J Mol Sci. 2021;22(10):5282. DOI:10.3390/ijms22105282.</mixed-citation><mixed-citation xml:lang="en">Chocarro L, Blanco E, Zuazo M, et al. Understanding LAG-3 signaling. Int J Mol Sci. 2021;22(10):5282. DOI:10.3390/ijms22105282.</mixed-citation></citation-alternatives></ref><ref id="cit7"><label>7</label><citation-alternatives><mixed-citation xml:lang="ru">Rubio-Infante N, Ramirez-F lores YA, Castillo EC, et al. A systematic review of the mechanisms involved in immune checkpoint inhibitors cardiotoxicity and challenges to improve clinical safety. Front Cell Dev Biol. 2022;10:851032. DOI:10.3389/fcell.2022.851032.</mixed-citation><mixed-citation xml:lang="en">Rubio-Infante N, Ramirez-F lores YA, Castillo EC, et al. A systematic review of the mechanisms involved in immune checkpoint inhibitors cardiotoxicity and challenges to improve clinical safety. Front Cell Dev Biol. 2022;10:851032. DOI:10.3389/fcell.2022.851032.</mixed-citation></citation-alternatives></ref><ref id="cit8"><label>8</label><citation-alternatives><mixed-citation xml:lang="ru">Ganesh S, Zhong P, Zhou X. Cardiotoxicity induced by immune checkpoint inhibitor: The complete insight into mechanisms, monitoring, diagnosis, and treatment. Front Cardiovasc Med. 2022;9:997660. DOI:10.3389/fcvm.2022.997660.</mixed-citation><mixed-citation xml:lang="en">Ganesh S, Zhong P, Zhou X. Cardiotoxicity induced by immune checkpoint inhibitor: The complete insight into mechanisms, monitoring, diagnosis, and treatment. Front Cardiovasc Med. 2022;9:997660. DOI:10.3389/fcvm.2022.997660.</mixed-citation></citation-alternatives></ref><ref id="cit9"><label>9</label><citation-alternatives><mixed-citation xml:lang="ru">Wei SC, Meijers WC, Axelrod ML, et al. A genetic mouse model recapitulates immune checkpoint inhibitor–associated myocarditis and supports a mechanismbased therapeutic intervention. Cancer Discov. 2021;11(3):614625. DOI:10.1158/2159-8290.CD-20-0856.</mixed-citation><mixed-citation xml:lang="en">Wei SC, Meijers WC, Axelrod ML, et al. A genetic mouse model recapitulates immune checkpoint inhibitor–associated myocarditis and supports a mechanismbased therapeutic intervention. Cancer Discov. 2021;11(3):614625. DOI:10.1158/2159-8290.CD-20-0856.</mixed-citation></citation-alternatives></ref><ref id="cit10"><label>10</label><citation-alternatives><mixed-citation xml:lang="ru">Thuny F, Naidoo J, Neilan TG. Cardiovascular complications of immune checkpoint inhibitors for cancer. Eur Heart J. 2022;43(42):4458-4468. DOI:10.1093/eurheartj/ehac456.</mixed-citation><mixed-citation xml:lang="en">Thuny F, Naidoo J, Neilan TG. Cardiovascular complications of immune checkpoint inhibitors for cancer. Eur Heart J. 2022;43(42):4458-4468. DOI:10.1093/eurheartj/ehac456.</mixed-citation></citation-alternatives></ref><ref id="cit11"><label>11</label><citation-alternatives><mixed-citation xml:lang="ru">Moslehi J, Lichtman AH, Sharpe AH, et al. Immune checkpoint inhibitor–associated myocarditis: manifestations and mechanisms. J Clin Invest. 2021;131(5):e145186. DOI:10.1172/JCI145186.</mixed-citation><mixed-citation xml:lang="en">Moslehi J, Lichtman AH, Sharpe AH, et al. Immune checkpoint inhibitor–associated myocarditis: manifestations and mechanisms. J Clin Invest. 2021;131(5):e145186. DOI:10.1172/JCI145186.</mixed-citation></citation-alternatives></ref><ref id="cit12"><label>12</label><citation-alternatives><mixed-citation xml:lang="ru">Gallegos C, Rottmann D, Nguyen VQ, et al. Myocarditis with checkpoint inhibitor immunotherapy: case report of late gadolinium enhancement on cardiac magnetic resonance with pathology correlate. Eur Heart J Case Rep. 2019;3(1):yty149. DOI:10.1093/ehjcr/yty149.</mixed-citation><mixed-citation xml:lang="en">Gallegos C, Rottmann D, Nguyen VQ, et al. Myocarditis with checkpoint inhibitor immunotherapy: case report of late gadolinium enhancement on cardiac magnetic resonance with pathology correlate. Eur Heart J Case Rep. 2019;3(1):yty149. DOI:10.1093/ehjcr/yty149.</mixed-citation></citation-alternatives></ref><ref id="cit13"><label>13</label><citation-alternatives><mixed-citation xml:lang="ru">Lim SY, Lee JH, Gide, TN, et al. Circulating cytokines predict immune-r elated toxicity in melanoma patients receiving anti-PD-1–based immunotherapy. Clin Cancer Res. 2019;25(5):1557-1563. DOI:10.1158/1078-0432.CCR-18-2795.</mixed-citation><mixed-citation xml:lang="en">Lim SY, Lee JH, Gide, TN, et al. Circulating cytokines predict immune-r elated toxicity in melanoma patients receiving anti-PD-1–based immunotherapy. Clin Cancer Res. 2019;25(5):1557-1563. DOI:10.1158/1078-0432.CCR-18-2795.</mixed-citation></citation-alternatives></ref><ref id="cit14"><label>14</label><citation-alternatives><mixed-citation xml:lang="ru">Yin J, Yao Z, Pan J, et al. Immune checkpoint inhibitor‐related myocarditis in thymic epithelial tumors: Recent progress and perspectives. MedComm– Oncology. 2023;2(2):e31. DOI:10.1002/mog2.31.</mixed-citation><mixed-citation xml:lang="en">Yin J, Yao Z, Pan J, et al. Immune checkpoint inhibitor‐related myocarditis in thymic epithelial tumors: Recent progress and perspectives. MedComm– Oncology. 2023;2(2):e31. DOI:10.1002/mog2.31.</mixed-citation></citation-alternatives></ref><ref id="cit15"><label>15</label><citation-alternatives><mixed-citation xml:lang="ru">Won T, Kalinoski HM, Wood MK, et al. Cardiac myosin-s pecific autoimmune T cells contribute to immune-checkpoint-inhibitor-associated myocarditis. Cell Rep. 2022;41(6):111611. DOI:10.1016/j.celrep.2022.111611.</mixed-citation><mixed-citation xml:lang="en">Won T, Kalinoski HM, Wood MK, et al. Cardiac myosin-s pecific autoimmune T cells contribute to immune-checkpoint-inhibitor-associated myocarditis. Cell Rep. 2022;41(6):111611. DOI:10.1016/j.celrep.2022.111611.</mixed-citation></citation-alternatives></ref><ref id="cit16"><label>16</label><citation-alternatives><mixed-citation xml:lang="ru">Khunger A, Battel L, Wadhawan A, et al. New insights into mechanisms of immune checkpoint inhibitor-induced cardiovascular toxicity. Curr Oncol Rep. 2020;22(7):65. DOI:10.1007/s11912-020-00925-8.</mixed-citation><mixed-citation xml:lang="en">Khunger A, Battel L, Wadhawan A, et al. New insights into mechanisms of immune checkpoint inhibitor-induced cardiovascular toxicity. Curr Oncol Rep. 2020;22(7):65. DOI:10.1007/s11912-020-00925-8.</mixed-citation></citation-alternatives></ref><ref id="cit17"><label>17</label><citation-alternatives><mixed-citation xml:lang="ru">Michel L., Helfrich I., Hendgen-Cotta UB., et al. Targeting early stages of cardiotoxicity from anti-P D1 immune checkpoint inhibitor therapy. Eur Heart J. 2022;43(4):316-329. DOI:10.1093/eurheartj/ehab430.</mixed-citation><mixed-citation xml:lang="en">Michel L., Helfrich I., Hendgen-Cotta UB., et al. Targeting early stages of cardiotoxicity from anti-P D1 immune checkpoint inhibitor therapy. Eur Heart J. 2022;43(4):316-329. DOI:10.1093/eurheartj/ehab430.</mixed-citation></citation-alternatives></ref><ref id="cit18"><label>18</label><citation-alternatives><mixed-citation xml:lang="ru">Li X, Peng W, Wu J, et al. Advances in immune checkpoint inhibitors induced-cardiotoxicity. Front Immunol. 2023;14:1130438. DOI:10.3389/fimmu.2023.1130438.</mixed-citation><mixed-citation xml:lang="en">Li X, Peng W, Wu J, et al. Advances in immune checkpoint inhibitors induced-cardiotoxicity. Front Immunol. 2023;14:1130438. DOI:10.3389/fimmu.2023.1130438.</mixed-citation></citation-alternatives></ref><ref id="cit19"><label>19</label><citation-alternatives><mixed-citation xml:lang="ru">Gil-Cruz C, Perez-S hibayama C, De Martin A, et al. Microbiota-derived peptide mimics drive lethal inflammatory cardiomyopathy. Science. 2019; 366(6467):881-886. DOI:10.1126/science.aav3487.</mixed-citation><mixed-citation xml:lang="en">Gil-Cruz C, Perez-S hibayama C, De Martin A, et al. Microbiota-derived peptide mimics drive lethal inflammatory cardiomyopathy. Science. 2019; 366(6467):881-886. DOI:10.1126/science.aav3487.</mixed-citation></citation-alternatives></ref><ref id="cit20"><label>20</label><citation-alternatives><mixed-citation xml:lang="ru">Nishimura H, Okazaki T, Tanaka Y, et al. Autoimmune dilated cardiomyopathy in PD-1 receptor-deficient mice. Science. 2001;291(5502):319-322. DOI:10.1126/science.291.5502.319.</mixed-citation><mixed-citation xml:lang="en">Nishimura H, Okazaki T, Tanaka Y, et al. Autoimmune dilated cardiomyopathy in PD-1 receptor-deficient mice. Science. 2001;291(5502):319-322. DOI:10.1126/science.291.5502.319.</mixed-citation></citation-alternatives></ref><ref id="cit21"><label>21</label><citation-alternatives><mixed-citation xml:lang="ru">Okazaki T., Tanaka Y., Nishio R., et al. Autoantibodies against cardiac tro ponin I are responsible for dilated cardiomyopathy in PD-1-deficient mice. Nat Med. 2003;9(12):1477-1483. DOI:10.1038/nm955.</mixed-citation><mixed-citation xml:lang="en">Okazaki T., Tanaka Y., Nishio R., et al. Autoantibodies against cardiac tro ponin I are responsible for dilated cardiomyopathy in PD-1-deficient mice. Nat Med. 2003;9(12):1477-1483. DOI:10.1038/nm955.</mixed-citation></citation-alternatives></ref><ref id="cit22"><label>22</label><citation-alternatives><mixed-citation xml:lang="ru">Gergely TG, Kucsera D, Tóth VE, et al. Characterization of immune check point inhibitor‐induced cardiotoxicity reveals interleukin‐17A as a driver of cardiac dysfunction after anti‐PD‐1 treatment. Br J Pharmacol. 2023;180(6):740-761. DOI:10.1111/bph.15984.</mixed-citation><mixed-citation xml:lang="en">Gergely TG, Kucsera D, Tóth VE, et al. Characterization of immune check point inhibitor‐induced cardiotoxicity reveals interleukin‐17A as a driver of cardiac dysfunction after anti‐PD‐1 treatment. Br J Pharmacol. 2023;180(6):740-761. DOI:10.1111/bph.15984.</mixed-citation></citation-alternatives></ref><ref id="cit23"><label>23</label><citation-alternatives><mixed-citation xml:lang="ru">Хегай И. М., Трунина И. И., Чеботарева Т. А., и др. Роль иммунной системы в развитии и прогрессировании вирусного повреждения миокарда. Российский вестник перинатологии и педиатрии. 2021;66(3):27-33]. DOI:10.21508/1027-4065-2021-66-3-27-33.</mixed-citation><mixed-citation xml:lang="en">Khegai I. M., Trunina I. I., Chebotareva T. A., et al. Immune system in development and progression of viral myocardial damage. Rossiyskiy Vestnik Perinatologii i Pediatrii (Russian Bulletin of Perinatology and Pediatrics). 2021; 66:(3): 27–33 (in Russ). DOI:10.21508/1027-4065-2021-66-3-27-33.</mixed-citation></citation-alternatives></ref><ref id="cit24"><label>24</label><citation-alternatives><mixed-citation xml:lang="ru">Намитоков А. М., Зафираки В. К., Донец Е. К., и др. Агрессивное течение атеросклероза при гиперлипопротеинемии (а): серия клинических случаев. Рациональная Фармакотерапия в Кардиологии. 2023;19(6):591-596]. DOI:10.20996/1819-6446-2023-2873.</mixed-citation><mixed-citation xml:lang="en">Namitokov A. M., Zaphiraki V. K., Donets E. K., et al. Aggressive course of atherosclerosis in hyperlipoproteinemia (a): a case series. Rational Pharmacotherapy in Cardiology. 2023;19(6):591-596. (In Russ.) [Намитоков А. М., Зафираки В. К., Донец Е. К., и др. Агрессивное течение атеросклероза при гиперлипопротеинемии (а): серия клинических случаев. Рациональная Фармакотерапия в Кардиологии. 2023;19(6):591-596]. DOI:10.20996/1819-6446-2023-2873.</mixed-citation></citation-alternatives></ref><ref id="cit25"><label>25</label><citation-alternatives><mixed-citation xml:lang="ru">Bu DX, Tarrio M, Maganto-Garcia E, et al. Impairment of the programmed cell death-1 pathway increases atherosclerotic lesion development and inflammation. Arterioscler Thromb Vasc Biol. 2011;31(5):1100-1107. DOI:10.1161/ATVBAHA.111.224709.</mixed-citation><mixed-citation xml:lang="en">Bu DX, Tarrio M, Maganto-Garcia E, et al. Impairment of the programmed cell death-1 pathway increases atherosclerotic lesion development and inflammation. Arterioscler Thromb Vasc Biol. 2011;31(5):1100-1107. DOI:10.1161/ATVBAHA.111.224709.</mixed-citation></citation-alternatives></ref><ref id="cit26"><label>26</label><citation-alternatives><mixed-citation xml:lang="ru">Poels K, van Leent MM, Reiche ME, et al. Antibody-mediated inhibition of CTLA4 aggravates atherosclerotic plaque inflammation and progression in hyperlipidemic mice. Cells. 2020;9(9):1987. DOI:10.3390/cells9091987.</mixed-citation><mixed-citation xml:lang="en">Poels K, van Leent MM, Reiche ME, et al. Antibody-mediated inhibition of CTLA4 aggravates atherosclerotic plaque inflammation and progression in hyperlipidemic mice. Cells. 2020;9(9):1987. DOI:10.3390/cells9091987.</mixed-citation></citation-alternatives></ref><ref id="cit27"><label>27</label><citation-alternatives><mixed-citation xml:lang="ru">Suero-Abreu GA, Zanni MV, Neilan TG. Atherosclerosis with immune checkpoint inhibitor therapy: evidence, diagnosis, and management: JACC: CardioOncology State-of-the-Art Review. JACC CardioOncol. 2022;4(5):598615. DOI:10.1016/j.jaccao.2022.11.011.</mixed-citation><mixed-citation xml:lang="en">Suero-Abreu GA, Zanni MV, Neilan TG. Atherosclerosis with immune checkpoint inhibitor therapy: evidence, diagnosis, and management: JACC: CardioOncology State-of-the-Art Review. JACC CardioOncol. 2022;4(5):598615. DOI:10.1016/j.jaccao.2022.11.011.</mixed-citation></citation-alternatives></ref><ref id="cit28"><label>28</label><citation-alternatives><mixed-citation xml:lang="ru">Fernandez DM, Rahman AH, Fernandez NF, et al. Single-cell immune landscape of human atherosclerotic plaques. Nat Med. 2019;25(10):15761588. DOI:10.1038/s41591-019-0590-4.</mixed-citation><mixed-citation xml:lang="en">Fernandez DM, Rahman AH, Fernandez NF, et al. Single-cell immune landscape of human atherosclerotic plaques. Nat Med. 2019;25(10):15761588. DOI:10.1038/s41591-019-0590-4.</mixed-citation></citation-alternatives></ref><ref id="cit29"><label>29</label><citation-alternatives><mixed-citation xml:lang="ru">Crout TM, Lennep DS, Kishore S, Majithia V. Systemic vasculitis associated with immune check point inhibition: analysis and review. Curr Rheumatol Rep. 2019;21(6):28. DOI:10.1007/s11926-019-0828-7.</mixed-citation><mixed-citation xml:lang="en">Crout TM, Lennep DS, Kishore S, Majithia V. Systemic vasculitis associated with immune check point inhibition: analysis and review. Curr Rheumatol Rep. 2019;21(6):28. DOI:10.1007/s11926-019-0828-7.</mixed-citation></citation-alternatives></ref><ref id="cit30"><label>30</label><citation-alternatives><mixed-citation xml:lang="ru">Zarifa A, Kim JW, Lopez-Mattei J, et al. Cardiac Toxicities Associated with Immune Checkpoints Inhibitors: Mechanisms, Manifestations and Management. Korean Circ J. 2021;51(7):579-597. DOI:10.4070/kcj.2021.0089.</mixed-citation><mixed-citation xml:lang="en">Zarifa A, Kim JW, Lopez-Mattei J, et al. Cardiac Toxicities Associated with Immune Checkpoints Inhibitors: Mechanisms, Manifestations and Management. Korean Circ J. 2021;51(7):579-597. DOI:10.4070/kcj.2021.0089.</mixed-citation></citation-alternatives></ref><ref id="cit31"><label>31</label><citation-alternatives><mixed-citation xml:lang="ru">Nykl R, Fischer O, Vykoupil K, et al. A unique reason for coronary spasm causing temporary ST elevation myocardial infarction (inferior STEMI)– systemic inflammatory response syndrome after use of pembrolizumab. Arch Med Sci Atheroscler Dis. 2017;2:e100-e102. DOI:10.5114/amsad.2017.72531.</mixed-citation><mixed-citation xml:lang="en">Nykl R, Fischer O, Vykoupil K, et al. A unique reason for coronary spasm causing temporary ST elevation myocardial infarction (inferior STEMI)– systemic inflammatory response syndrome after use of pembrolizumab. Arch Med Sci Atheroscler Dis. 2017;2:e100-e102. DOI:10.5114/amsad.2017.72531.</mixed-citation></citation-alternatives></ref><ref id="cit32"><label>32</label><citation-alternatives><mixed-citation xml:lang="ru">Otsu K, Tajiri K, Sakai S, et al. Vasospastic angina following immune check - point blockade. Eur Heart J. 2020;41(17):1702. DOI:10.1093/eurheartj/ehz796.</mixed-citation><mixed-citation xml:lang="en">Otsu K, Tajiri K, Sakai S, et al. Vasospastic angina following immune check - point blockade. Eur Heart J. 2020;41(17):1702. DOI:10.1093/eurheartj/ehz796.</mixed-citation></citation-alternatives></ref><ref id="cit33"><label>33</label><citation-alternatives><mixed-citation xml:lang="ru">Kumamoto T, Kawano H, Kurobe M., et al. Vasospastic Angina: An Immune-related Adverse Event. Internal Medicine. 2022;61(13):1983-1986. DOI:10.2169/internalmedicine.8540-21</mixed-citation><mixed-citation xml:lang="en">Kumamoto T, Kawano H, Kurobe M., et al. Vasospastic Angina: An Immune-related Adverse Event. Internal Medicine. 2022;61(13):1983-1986. DOI:10.2169/internalmedicine.8540-21</mixed-citation></citation-alternatives></ref><ref id="cit34"><label>34</label><citation-alternatives><mixed-citation xml:lang="ru">Fonseca M, Cheng E, Do D, et al. Bradyarrhythmias in Cardio-Oncology. South Asian J Cancer. 2021;10(03):195-210. DOI:10.1055/s-0041-1731907.</mixed-citation><mixed-citation xml:lang="en">Fonseca M, Cheng E, Do D, et al. Bradyarrhythmias in Cardio-Oncology. South Asian J Cancer. 2021;10(03):195-210. DOI:10.1055/s-0041-1731907.</mixed-citation></citation-alternatives></ref><ref id="cit35"><label>35</label><citation-alternatives><mixed-citation xml:lang="ru">Waliany S, Lee D, Witteles RM, et al. Immune checkpoint inhibitor cardiotoxicity: understanding basic mechanisms and clinical characteristics and finding a cure. Annu Rev Pharmacol Toxicol. 2021;61:113-134. DOI:10.1146/annurev-pharmtox-010919-023451.</mixed-citation><mixed-citation xml:lang="en">Waliany S, Lee D, Witteles RM, et al. Immune checkpoint inhibitor cardiotoxicity: understanding basic mechanisms and clinical characteristics and finding a cure. Annu Rev Pharmacol Toxicol. 2021;61:113-134. DOI:10.1146/annurev-pharmtox-010919-023451.</mixed-citation></citation-alternatives></ref><ref id="cit36"><label>36</label><citation-alternatives><mixed-citation xml:lang="ru">Johnson DB, Balko JM, Compton ML, et al. Fulminant myocarditis with combination immune checkpoint blockade. N Engl J Med. 2016;375(18): 1749-1755. DOI:10.1056/NEJMoa1609214.</mixed-citation><mixed-citation xml:lang="en">Johnson DB, Balko JM, Compton ML, et al. Fulminant myocarditis with combination immune checkpoint blockade. N Engl J Med. 2016;375(18): 1749-1755. DOI:10.1056/NEJMoa1609214.</mixed-citation></citation-alternatives></ref><ref id="cit37"><label>37</label><citation-alternatives><mixed-citation xml:lang="ru">Lyon AR, Yousaf N, Battisti NML, et al. Immune checkpoint inhibitors and cardiovascular toxicity. Lancet Oncol. 2018;19(9):e447-e458. DOI:10.1016/S1470-2045(18)30457-1.</mixed-citation><mixed-citation xml:lang="en">Lyon AR, Yousaf N, Battisti NML, et al. Immune checkpoint inhibitors and cardiovascular toxicity. Lancet Oncol. 2018;19(9):e447-e458. DOI:10.1016/S1470-2045(18)30457-1.</mixed-citation></citation-alternatives></ref><ref id="cit38"><label>38</label><citation-alternatives><mixed-citation xml:lang="ru">Safi M, Ahmed H, Al-Azab M, et al. PD-1/PDL-1 inhibitors and cardiotoxicity; molecular, etiological and management outlines. J Adv Res. 2021;29:45-54. DOI:10.1016/j.jare.2020.09.006.</mixed-citation><mixed-citation xml:lang="en">Safi M, Ahmed H, Al-Azab M, et al. PD-1/PDL-1 inhibitors and cardiotoxicity; molecular, etiological and management outlines. J Adv Res. 2021;29:45-54. DOI:10.1016/j.jare.2020.09.006.</mixed-citation></citation-alternatives></ref><ref id="cit39"><label>39</label><citation-alternatives><mixed-citation xml:lang="ru">Mascolo A, Sportiello L, Rafaniello C, et al. Do immune checkpoint inhibitors share the same pharmacological feature in the risk of cardiac arrhythmias? Biomed Pharmacother. 2023;164:114912. DOI:10.1016/j.biopha.2023.114912.</mixed-citation><mixed-citation xml:lang="en">Mascolo A, Sportiello L, Rafaniello C, et al. Do immune checkpoint inhibitors share the same pharmacological feature in the risk of cardiac arrhythmias? Biomed Pharmacother. 2023;164:114912. DOI:10.1016/j.biopha.2023.114912.</mixed-citation></citation-alternatives></ref><ref id="cit40"><label>40</label><citation-alternatives><mixed-citation xml:lang="ru">Altan M, Toki MI, Gettinger SN, et al. Immune checkpoint inhibitor– associated pericarditis. J Thorac Oncol. 2019;14(6):1102-1108. DOI:10.1016/j.jtho.2019.02.026.</mixed-citation><mixed-citation xml:lang="en">Altan M, Toki MI, Gettinger SN, et al. Immune checkpoint inhibitor– associated pericarditis. J Thorac Oncol. 2019;14(6):1102-1108. DOI:10.1016/j.jtho.2019.02.026.</mixed-citation></citation-alternatives></ref><ref id="cit41"><label>41</label><citation-alternatives><mixed-citation xml:lang="ru">Shalata W, Steckbeck R, Abu Salman A, et al. Perimyocarditis Associated with Immune Checkpoint Inhibitors: A Case Report and Review of the Literature. Medicina (Kaunas). 2024;60(2):224. DOI:10.3390/medicina60020224.</mixed-citation><mixed-citation xml:lang="en">Shalata W, Steckbeck R, Abu Salman A, et al. Perimyocarditis Associated with Immune Checkpoint Inhibitors: A Case Report and Review of the Literature. Medicina (Kaunas). 2024;60(2):224. DOI:10.3390/medicina60020224.</mixed-citation></citation-alternatives></ref><ref id="cit42"><label>42</label><citation-alternatives><mixed-citation xml:lang="ru">Mocan-Hognogi DL, Trancǎ S, Farcaş AD, et al. Immune checkpoint inhibitors and the heart. Front Cardiovasc Med. 2021;8:726426. DOI:10.3389/fcvm.2021.726426.</mixed-citation><mixed-citation xml:lang="en">Mocan-Hognogi DL, Trancǎ S, Farcaş AD, et al. Immune checkpoint inhibitors and the heart. Front Cardiovasc Med. 2021;8:726426. DOI:10.3389/fcvm.2021.726426.</mixed-citation></citation-alternatives></ref><ref id="cit43"><label>43</label><citation-alternatives><mixed-citation xml:lang="ru">Paluri RK, Pulipati Y, Regalla DKR. Immune Checkpoint Inhibitors and Their Cardiovascular Adverse Effects. Oncol Rev. 2023;17:11456. DOI:10.3389/or.2023.11456.</mixed-citation><mixed-citation xml:lang="en">Paluri RK, Pulipati Y, Regalla DKR. Immune Checkpoint Inhibitors and Their Cardiovascular Adverse Effects. Oncol Rev. 2023;17:11456. DOI:10.3389/or.2023.11456.</mixed-citation></citation-alternatives></ref><ref id="cit44"><label>44</label><citation-alternatives><mixed-citation xml:lang="ru">Марчев С., Веков Т. Рациональная фармакотерапия при кардио миопатии Такоцубо. Рациональная Фармакотерапия в Кардиологии. 2012;8(6):777-780]. DOI:10.20996/1819-6446-2012-8-6-777-780.</mixed-citation><mixed-citation xml:lang="en">Marchev S., Vekov T. Rational pharmacotherapy in Takotsubo cardiomyo pathy. Rational Pharmacotherapy in Cardiology. 2012;8(6):777-780. (In Russ.) DOI:10.20996/1819-6446-2012-8-6-777-780.</mixed-citation></citation-alternatives></ref><ref id="cit45"><label>45</label><citation-alternatives><mixed-citation xml:lang="ru">Palaskas N, Morgan J, Daigle T, et al. Targeted cancer therapies with pericardial effusions requiring pericardiocentesis focusing on immune checkpoint inhibitors. Am J Cardiol. 2019;123(8):1351-1357. DOI:10.1016/j.amjcard.2019.01.013.</mixed-citation><mixed-citation xml:lang="en">Palaskas N, Morgan J, Daigle T, et al. Targeted cancer therapies with pericardial effusions requiring pericardiocentesis focusing on immune checkpoint inhibitors. Am J Cardiol. 2019;123(8):1351-1357. DOI:10.1016/j.amjcard.2019.01.013.</mixed-citation></citation-alternatives></ref><ref id="cit46"><label>46</label><citation-alternatives><mixed-citation xml:lang="ru">Trontzas IP, Vathiotis IA, Kyriakoulis KG, et al; ImmunoTTS Collaborative Group. Takotsubo Cardiomyopathy in Cancer Patients Treated with Immune Checkpoint Inhibitors: A Systematic Review and Meta-S ummary of Included Cases. Cancers (Basel). 2023;15(9):2637. DOI:10.3390/cancers15092637.</mixed-citation><mixed-citation xml:lang="en">Trontzas IP, Vathiotis IA, Kyriakoulis KG, et al; ImmunoTTS Collaborative Group. Takotsubo Cardiomyopathy in Cancer Patients Treated with Immune Checkpoint Inhibitors: A Systematic Review and Meta-S ummary of Included Cases. Cancers (Basel). 2023;15(9):2637. DOI:10.3390/cancers15092637.</mixed-citation></citation-alternatives></ref><ref id="cit47"><label>47</label><citation-alternatives><mixed-citation xml:lang="ru">Guha A, Dey AK, Miller E, et al. Abstract 12013: Trends in Reported Cardiovascular Disease and Hospitalizations in Cancer Patients-Cardio-oncology Patterns Over 14-year From Two Nationally Representative Datas ets. Circulation. 2019;140(Suppl 1):A12013.</mixed-citation><mixed-citation xml:lang="en">Guha A, Dey AK, Miller E, et al. Abstract 12013: Trends in Reported Cardiovascular Disease and Hospitalizations in Cancer Patients-Cardio-oncology Patterns Over 14-year From Two Nationally Representative Datas ets. Circulation. 2019;140(Suppl 1):A12013.</mixed-citation></citation-alternatives></ref><ref id="cit48"><label>48</label><citation-alternatives><mixed-citation xml:lang="ru">Polizzotti B. D., Arab S., Kuhn B. Intrapericardial delivery of gelfoam enables the targeted delivery of periostine peptide after myocardial infarction by inducing fibrin clot formation. PLoS One 2012;7: e36788. DOI:10.1371/journal.pone.0036788.</mixed-citation><mixed-citation xml:lang="en">Polizzotti B. D., Arab S., Kuhn B. Intrapericardial delivery of gelfoam enables the targeted delivery of periostine peptide after myocardial infarction by inducing fibrin clot formation. PLoS One 2012;7: e36788. DOI:10.1371/journal.pone.0036788.</mixed-citation></citation-alternatives></ref></ref-list><fn-group><fn fn-type="conflict"><p>The authors declare that there are no conflicts of interest present.</p></fn></fn-group></back></article>
