A SIGNIFICANTLY increased risk of heart failure (HF) in cancer patients receiving PD-1 immune checkpoint inhibitors (ICIs) has been highlighted in a new study, particularly among those with a history of ischaemic heart disease.
ICIs targeting the programmed cell death protein-1 (PD-1) pathway have transformed cancer care, but concerns are growing regarding their cardiovascular safety profile. In this study, researchers combined preclinical and clinical data to investigate whether prior cardiac ischaemia amplifies the cardiotoxic effects of anti-PD-1 therapy, and whether this risk could be mitigated.
Preclinical Model Shows Increased Cardiac Inflammation
In a preclinical mouse model, transient cardiac ischaemia was induced and allowed to recover before treatment with anti-PD-1 therapy. Mice with prior ischaemic injury developed marked cardiac dysfunction following PD-1 inhibition, accompanied by increased infiltration of T cells and macrophages and elevated pro-inflammatory cytokine expression. In contrast, mice without prior cardiac injury experienced significantly less inflammation and preserved cardiac function under the same treatment.
Importantly, co-treatment with abatacept, a T-cell co-stimulation blocker, prevented these adverse effects. Mice receiving abatacept alongside anti-PD-1 therapy maintained normal cardiac function and demonstrated reduced inflammatory responses, suggesting a potential protective strategy against ICI-induced cardiotoxicity.
To support these findings, the investigators conducted a retrospective cohort study of 1,671 cancer patients treated with PD-1 inhibitors. Over a median follow-up of 332 days, 109 patients (6.5%) developed new-onset HF. Statistical analysis revealed that patients with a prior history of ischaemic heart disease had more than double the risk of developing HF following ICI therapy (odds ratio 2.11; 95% CI 1.05–4.2; p=0.033), compared with those without such history.
Findings Support Need for Cardiac Monitoring in High-Risk Patients
These findings provide clinically relevant evidence that pre-existing cardiac injury is a key risk factor for ICI-associated HF. The consistency between experimental and patient data strengthens the biological plausibility of the observed association.
The authors conclude that patients with a history of ischaemic heart disease may require closer cardiac monitoring when undergoing PD-1 inhibitor therapy. Furthermore, the protective effects of abatacept observed in the preclinical model warrant further investigation in clinical settings.
Overall, the study underscores the need for a more personalised approach to cancer immunotherapy, balancing oncological benefits with cardiovascular risk assessment and management.
Reference
Gergely TG 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.
Featured image: Towfiqu Barbhuiya
