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However, their use often leads to cardiovascular adverse effects, including cardiac dysfunction. Here, we hypothesized that a prior cardiac ischaemic injury could exacerbate cardiac dysfunction due to anti-programmed death protein 1 (PD-1) treatment. Furthermore, we investigated whether abatacept, a T-cell costimulation blocker, could ameliorate the ICI-induced cardiotoxicity in a pre-clinical model.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and results<\/jats:title>\n                    <jats:p>In a pre-clinical study, mice were treated with isoprenaline or control to induce reversible cardiac ischaemia. After 16 weeks of follow-up, recovery of cardiac function was confirmed via echocardiography, and mice from both groups were randomly treated with isotype control, anti-PD-1, or anti-PD-1 combined with abatacept, for 2 further weeks. Mice with prior ischaemic injury and anti-PD-1 treatment showed cardiac dysfunction with increased infiltration of T cells and macrophages and elevated expression of pro-inflammatory cytokines. Conversely, cardiac dysfunction and inflammation were less pronounced after anti-PD-1 treatment in mice without prior ischaemic injury. Mice with concomitant abatacept treatment exhibited normal cardiac function and alleviated pro-inflammatory response. In a parallel single-centre retrospective clinical cohort study, 1671 cancer patients receiving PD-1 inhibitors were analysed. Cases were defined as patients who developed incident heart failure (HF) after ICI initiation with a primary aim to test whether pre-existing ischaemic heart disease was associated with an increased risk for HF development post-ICI therapy. Sensitivity analyses included propensity score matching and comparison with non-ICI-treated cancer patients. Among ICI-treated patients, 109 (6.5%) developed HF over a median follow-up of 332 days. Multivariable logistic regression of the matched population showed increased odds of incident HF in patients with prior ischaemic cardiac events (odds ratio 2.11, 95% confidence interval 1.05\u20134.2, P = 0.033).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>In mice, induction of cardiac inflammation and dysfunction by anti-PD-1 therapy was potentiated by prior transient ischaemic cardiac injury, which was ameliorated by abatacept cotreatment. Cancer patients with pre-existing ischaemic heart disease may be at greater risk for developing ICI-induced new-onset HF. Based on our findings, cardiac surveillance should be considered in patients starting ICI therapy with a prior history of ischaemic heart disease.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/cvr\/cvag085","type":"journal-article","created":{"date-parts":[[2026,4,21]],"date-time":"2026-04-21T11:27:05Z","timestamp":1776770825000},"page":"1055-1069","source":"Crossref","is-referenced-by-count":0,"title":["Inhibition of the programmed death protein 1 immune checkpoint and the development of heart failure in the presence of prior cardiac ischaemia"],"prefix":"10.1093","volume":"122","author":[{"given":"Tam\u00e1s G","family":"Gergely","sequence":"first","affiliation":[{"name":"Department of Pharmacology and Pharmacotherapy, Semmelweis University , Budapest 1089 ,","place":["Hungary"]},{"name":"Center for Pharmacology and Drug Research & Development, Semmelweis University , Budapest 1089 ,","place":["Hungary"]},{"name":"HCEMM-SU Cardiometabolic Immunology Research Group , Budapest 1089, Hungary"},{"name":"MTA-SE Momentum Cardio-Oncology and Cardioimmunology Research Group , Budapest 1089, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zs\u00f3fia D","family":"Drobni","sequence":"additional","affiliation":[{"name":"Heart and Vascular Center, Semmelweis University , Budapest 1122 ,","place":["Hungary"]},{"name":"Cardiovascular Imaging Research Center (CIRC), Department of Radiology and Division of Cardiology, Massachusetts General Hospital, Harvard Medical School , Boston, MA 02114 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tam\u00e1s","family":"Kov\u00e1cs","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Pharmacotherapy, Semmelweis University , Budapest 1089 ,","place":["Hungary"]},{"name":"Center for Pharmacology and Drug Research & Development, Semmelweis University , Budapest 1089 ,","place":["Hungary"]},{"name":"HCEMM-SU Cardiometabolic Immunology Research Group , Budapest 1089, Hungary"},{"name":"MTA-SE Momentum Cardio-Oncology and Cardioimmunology Research Group , Budapest 1089, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nabil V","family":"Sayour","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Pharmacotherapy, Semmelweis University , Budapest 1089 ,","place":["Hungary"]},{"name":"Center for Pharmacology and Drug Research & Development, Semmelweis University , Budapest 1089 ,","place":["Hungary"]},{"name":"HCEMM-SU Cardiometabolic Immunology Research Group , Budapest 1089, Hungary"},{"name":"MTA-SE Momentum Cardio-Oncology and Cardioimmunology Research Group , Budapest 1089, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vikt\u00f3ria E","family":"T\u00f3th","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Pharmacotherapy, Semmelweis University , Budapest 1089 ,","place":["Hungary"]},{"name":"Center for Pharmacology and Drug Research & Development, Semmelweis University , Budapest 1089 ,","place":["Hungary"]},{"name":"HCEMM-SU Cardiometabolic Immunology Research Group , Budapest 1089, Hungary"},{"name":"MTA-SE Momentum Cardio-Oncology and Cardioimmunology Research Group , Budapest 1089, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-3870-9427","authenticated-orcid":false,"given":"M\u00e1rton S","family":"Kocsis","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Pharmacotherapy, Semmelweis University , Budapest 1089 ,","place":["Hungary"]},{"name":"Center for Pharmacology and Drug Research & Development, Semmelweis University , Budapest 1089 ,","place":["Hungary"]},{"name":"HCEMM-SU Cardiometabolic Immunology Research Group , Budapest 1089, Hungary"},{"name":"MTA-SE Momentum Cardio-Oncology and Cardioimmunology Research Group , Budapest 1089, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zs\u00f3fia","family":"On\u00f3di","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Pharmacotherapy, Semmelweis University , Budapest 1089 ,","place":["Hungary"]},{"name":"Center for Pharmacology and Drug Research & Development, Semmelweis University , Budapest 1089 ,","place":["Hungary"]},{"name":"HCEMM-SU Cardiometabolic Immunology Research Group , Budapest 1089, Hungary"},{"name":"MTA-SE Momentum Cardio-Oncology and Cardioimmunology Research Group , Budapest 1089, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G\u00e1bor M","family":"M\u00f3rotz","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Pharmacotherapy, Semmelweis University , Budapest 1089 ,","place":["Hungary"]},{"name":"Center for Pharmacology and Drug Research & Development, Semmelweis University , Budapest 1089 ,","place":["Hungary"]},{"name":"HCEMM-SU 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