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Evidence suggests that they may lead to immune-related adverse events, particularly when combined (e.g., anti-CTLA-4 plus anti-PD-1), sometimes resulting in severe conditions such as myocarditis. We aimed to investigate whether a previously sustained cardiac injury, such as pathological remodelling due to hypertension, is a prerequisite for ICI therapy-induced myocarditis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We evaluated the cardiotoxicity of ICIs in a hypertension (HTN) mouse model (C57BL\/6). Weekly doses were administered up to day 21 after the first administration. Our analysis encompassed the following parameters: (i) survival and cardiac pathological remodelling, (ii) cardiac function assessed using pressure-volume (PV)-loops, with brain natriuretic peptide (BNP) serving as a marker of haemodynamic dysfunction and (iii) cardiac inflammation (cytokine levels, infiltration, and cardiac antigen autoantibodies).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>After the first administration of ICI combined therapy, the treated HTN group showed a 30% increased mortality (P = 0.0002) and earlier signs of hypertrophy and pathological remodelling compared with the untreated HTN group. BNP (P = 0.01) and TNF-\u03b1 (&amp;lt;0.0001) increased 2.5- and 1.7-fold, respectively, in the treated group, while IL-6 (P = 0.8336) remained unchanged. Myocarditis only developed in the HTN group treated with ICIs on day 21 (score &amp;gt;3), characterised by T cell infiltration and increased cardiac antigen antibodies (86% showed a titre of 1:160). The control group treated with ICI was unaffected in any evaluated feature.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Our findings indicate that pre-existing sustained cardiac damage is a necessary condition for ICI-induced myocarditis.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/ehf2.14614","type":"journal-article","created":{"date-parts":[[2023,12,4]],"date-time":"2023-12-04T22:56:03Z","timestamp":1701730563000},"page":"1249-1257","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Previous Cardiovascular Injury is a Prerequisite for Immune Checkpoint Inhibitor-Associated Lethal Myocarditis in Mice"],"prefix":"10.1093","volume":"11","author":[{"given":"Nestor","family":"Rubio-Infante","sequence":"first","affiliation":[{"name":"Tecnologico de Monterrey, C\u00e1tedra de Cardiolog\u00eda y Medicina Vasular, Escuela de Medicina y Ciencias de la Salud , San Pedro Garza Garc\u00eda ,","place":["Mexico"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena Cristina","family":"Castillo","sequence":"additional","affiliation":[{"name":"Tecnologico de Monterrey, C\u00e1tedra de Cardiolog\u00eda y Medicina Vasular, Escuela de Medicina y Ciencias de la Salud , San Pedro Garza Garc\u00eda ,","place":["Mexico"]},{"name":"Tecnologico de Monterrey, Institute for Obesity Research, Hospital Zambrano Hellion, TecSalud , San Pedro Garza Garc\u00eda ,","place":["Mexico"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hugo","family":"Alves-Figueiredo","sequence":"additional","affiliation":[{"name":"Tecnologico de Monterrey, C\u00e1tedra de Cardiolog\u00eda y Medicina Vasular, Escuela de Medicina y Ciencias de la Salud , San Pedro Garza Garc\u00eda ,","place":["Mexico"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin","family":"Ramos-Gonz\u00e1lez","sequence":"additional","affiliation":[{"name":"Tecnologico de Monterrey, C\u00e1tedra de Cardiolog\u00eda y Medicina Vasular, Escuela de Medicina y Ciencias de la Salud , San Pedro Garza Garc\u00eda ,","place":["Mexico"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Felipe","family":"Salazar-Ram\u00edrez","sequence":"additional","affiliation":[{"name":"Tecnologico de Monterrey, C\u00e1tedra de Cardiolog\u00eda y Medicina Vasular, Escuela de Medicina y Ciencias de la Salud , San Pedro Garza Garc\u00eda ,","place":["Mexico"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Salas-Trevi\u00f1o","sequence":"additional","affiliation":[{"name":"Departamento de Histolog\u00eda, Facultad de Medicina, Universidad Aut\u00f3noma de Nuevo Le\u00f3n , Monterrey 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