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September 10, 2025

High incidence of immune checkpoint inhibitor therapy related subclinical cardiac dysfunction in patients with extracardiac immune related adverse events

RMRaluca MincuCardio-Oncology LZLisa ZimmerBroad Institute LLL LampeWest German Heart and Vascular Center Essen

Key Points

Patients with extracardiac immune related adverse events show a twofold higher incidence of mild cancer therapy related cardiac dysfunction.
Out of 2540 patients, 266 were analyzed, with 104 developing extracardiac irAEs and a relative risk of 2 for cardiac dysfunction.
This observational analysis utilized data from the Essen cardio-oncology Registry between 2018 and 2023, focusing on ICI therapy patients.
Significant implications for refining cardio-oncology surveillance protocols exist, particularly the need for routine echocardiography monitoring.

Abstract

Abstract Background Immune checkpoint inhibitor (ICI) therapy related cardiovascular toxicity (CTR-CVT) can significantly impact survival rate of cancer patients. The cardio-oncology guideline does not indicate serial echocardiography evaluations in cancer patients under ICI therapy, which may underestimate the incidence of CTR-CVT. Additionally, patients with extracardiac immune related adverse events (irAE) could present more CTR-CVT. Aim To determine the incidence of CTR-CVT in cancer patients with extracardiac irAEs under ICI therapy compared to control patients. CTR-CVT was diagnosed based on the cardio-oncology guideline definitions. Methods We have analyzed patients scheduled for ICI therapy from the EcoR (Essen cardio-oncology Registry) database from the local cardio-oncology unit between July 2018 and March 2023. Data was collected from the cardio-oncology consultations before ICI therapy start (baseline), at 6 weeks, 6 months and 12 months after therapy start. Patients were divided in two groups: patients diagnosed with extracardiac irAEs (group 1) and patients without extracardiac irAEs (group 2). Results Out of 2540 patients, we identified 266 individuals (61 ± 14 years, 40.6% female, 86.5% patients with melanoma, 62% with metastatic disease) scheduled for ICI therapy. 104 patients (37.5%) developed extracardiac irAEs (most frequent 15.4% hepatitis, 13.5 % colitis, 7.1 % thyroiditis) and were compared to 162 patients without extracardiac irAEs. Patients in the two groups were not significantly different regarding age, gender, cardiovascular risk factors and history of cardiovascular disease. Patients with extracardiac irAEs had a 2-fold higher risk of cancer therapy related cardiac dysfunction (CTRCD): relative risk (RR) 2 (95% CI 1.46, 2.76), p 0.001. Most of the patients (98.9%) suffered from a mild CTRCD, in 42% of cases diagnosed through a reduction in global longitudinal strain (GLS). The incidence of myocarditis was 10.5% in patients with extracardiac irAEs, compared to 0% in patients without extracardiac irAEs. There were no differences regarding the incidence of arrhythmia and vascular toxicity between the two groups. Conclusion Patients under ICI therapy with extracardiac irAEs show a twofold higher incidence of mild CTRCD and a high incidence of myocarditis. The early diagnostic of CTRCD cannot be performed in the absence of echocardiography data. Additionally, echocardiography data are listed as minor criteria for the diagnosis of ICI-myocarditis. This calls to a refining of cardio-oncology surveillance protocols in this patient group, urging the inclusion of echocardiography serial examination of patients with extracardiac irAEs under ICI therapy. The CTR-CVT is of utmost relevance for the prognosis of cancer survivors.

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