Inhibition of the PD-1 immune checkpoint and the development of heart failure in the presence of prior cardiac ischemia.
G, G.T., D, D.Z., Tamás, K., V, S.N., E, T.V., Márton, K., Zsófia, O., M, M.G., Andrea, K., A, Z.D., K, G.H., Jingyi, G., Nóra, F., Éva, P., I, B.E., I, Y.L., C, M.W., Béla, M., L, R.K., . . . V, V.Z. (2026). Inhibition of the PD-1 immune checkpoint and the development of heart failure in the presence of prior cardiac ischemia.. Cardiovasc Res. https://doi.org/10.1093/cvr/cvag085
G GT, D DZ, Tamás K, V SN, E TV, Márton K, et al. Inhibition of the PD-1 immune checkpoint and the development of heart failure in the presence of prior cardiac ischemia.. Cardiovasc Res. 2026; doi: 10.1093/cvr/cvag085
G GT, D DZ, Tamás K, et al. Inhibition of the PD-1 immune checkpoint and the development of heart failure in the presence of prior cardiac ischemia.[J]. Cardiovasc Res. 2026. DOI: 10.1093/cvr/cvag085.
@article{g2026,
author = {Gergely Tamás G and Drobni Zsófia D and Kovács Tamás and Sayour Nabil V and Tóth Viktória E and Kocsis Márton and Onódi Zsófia and Mórotz Gábor M and Kovács Andrea and Zlotoff Daniel A and Gilman Hannah K and Gong Jingyi and Fekete Nóra and Pállinger Éva and Buzás Edit I and Yousif Laura I and Meijers Wouter C and Merkely Béla and Reynolds Kerry L and Ferdinandy Péter and Neilan Tomas G and Varga Zoltán V},
title = {Inhibition of the PD-1 immune checkpoint and the development of heart failure in the presence of prior cardiac ischemia.},
journal = {Cardiovasc Res},
year = {2026},
doi = {10.1093/cvr/cvag085},
note = {PMID: 42019014},
}
TY - JOUR AU - Gergely Tamás G AU - Drobni Zsófia D AU - Kovács Tamás AU - Sayour Nabil V AU - Tóth Viktória E AU - Kocsis Márton AU - Onódi Zsófia AU - Mórotz Gábor M AU - Kovács Andrea AU - Zlotoff Daniel A AU - Gilman Hannah K AU - Gong Jingyi AU - Fekete Nóra AU - Pállinger Éva AU - Buzás Edit I AU - Yousif Laura I AU - Meijers Wouter C AU - Merkely Béla AU - Reynolds Kerry L AU - Ferdinandy Péter AU - Neilan Tomas G AU - Varga Zoltán V TI - Inhibition of the PD-1 immune checkpoint and the development of heart failure in the presence of prior cardiac ischemia. T2 - Cardiovasc Res PY - 2026 DO - 10.1093/cvr/cvag085 AN - PMID:42019014 ER -
Immune checkpoint inhibitors (ICI) have revolutionized cancer treatment. However, their use often leads to cardiovascular adverse effects, including cardiac dysfunction. Here, we hypothesized that a prior cardiac ischemic injury could exacerbate cardiac dysfunction due to anti-PD-1 treatment. Furthermore, we investigated whether abatacept, a T-cell co-stimulation blocker, could ameliorate the ICI-induced cardiotoxicity in a preclinical model. In a preclinical study, mice were treated with isoprenaline or control to induce reversible cardiac ischemia. 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 two further weeks. Mice with prior ischemic 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 ischemic injury. Mice with concomitant abatacept treatment exhibited normal cardiac function and alleviated pro-inflammatory response.In a parallel single-center retrospective clinical cohort study, 1,671 cancer patients receiving PD-1 inhibitors were analyzed. Cases were defined as patients who developed incident HF after ICI initiation with a primary aim to test whether pre-existing ischemic 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 ischemic cardiac events (OR 2.11 95%, CI 1.05-4.2, p=0.033). In mice, induction of cardiac inflammation and dysfunction by anti-PD1 therapy was potentiated by prior transient ischemic cardiac injury, which was ameliorated by abatacept co-treatment. Cancer patients with pre-existing ischemic 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 ischemic heart disease.