Cardiac dysfunction during immune checkpoint inhibitor therapy: association with extracardiac immune-related adverse events

BACKGROUND AND AIMS: With the increasing approval of immune checkpoint inhibitors (ICI) for cancer treatment, there is a rising incidence of potentially life-threatening cancer-therapy related cardiac dysfunction (CTRCD). Current 2022 European Society of Cardiology (ESC) guidelines on cardio-oncology recommend a single baseline transthoracic echocardiogram (TTE) for high-risk ICI-treated patients, potentially underestimating the incidence of CTRCD due to lack of follow-up assessments. This study aims to characterize the incidence of CTRCD in cancer patients undergoing ICI therapy using an intensified TTE surveillance approach and to investigate whether extracardiac immune-related adverse events (eirAEs) are associated with CTRCD. METHODS: We analysed patients scheduled for ICI therapy from the Essen Cardio-Oncology Registry (EcoR). Data were collected during cardio-oncology consultations at baseline, 6 weeks, 6 months, and 12 months. Patients with eirAEs were evaluated compared to patients without eirAEs. RESULTS: Among 2,540 cancer patients registered in EcoR until march 2023, 266 (61 ± 14 years, 40.6% female, 86.5% melanoma, 62% metastatic disease) were scheduled for ICI therapy. CTRCD was observed in 35.7% of patients, with 32.7% having asymptomatic mild CTRCD, 0.37% moderate CTRCD, and 2.63% developing heart failure with preserved ejection fraction (HFpEF). Patients with eirAEs had a twofold higher risk of CTRCD (relative risk [RR] 2.05, 95% CI: 1.49-2.83, p < 0.001) and a 66% increased risk of cardiovascular toxicity (RR 1.66, 95% CI 1.30-2.13, p < 0.001). CONCLUSIONS: ICI therapy is associated with a high prevalence of CTRCD, underscoring the importance of serial echocardiography evaluation, particularly for patients with eirAEs. Enhanced cardio-oncology surveillance is crucial for improving patient outcomes and survival.