Cardiac biomarkers for cardiovascular events in patients receiving immune checkpoint inhibitor therapy

Lars Michel (Essen)1, R. Mincu (Essen)1, F. Bühning (Essen)1, J. Vogel (Essen)1, S. Korste (Essen)1, E. Haj-Yehia (Essen)1, T. Rassaf (Essen)1, M. Totzeck (Essen)1

1Universitätsklinikum Essen Klinik für Kardiologie und Angiologie Essen, Deutschland


Background: Immune checkpoint inhibitors (ICI) have transformed advanced cancer treatment, yet they are associated with various cardiovascular (CV) adverse events. Recent data reveal a higher incidence of CV adverse events than previously recognized. Robust diagnostic tools are crucial for cardio-oncological monitoring. Biomarkers show promise in improving diagnostic and prognostic assessments, but prior studies primarily focused on ICI-related myocarditis. This study aims to assess the relationship between cardiac biomarkers and the entire spectrum of CV adverse events during ICI therapy.

Methods: The analysis included all consecutive patients from the Essen cardio-oncology Registry (EcoR) receiving ICI therapy. Non-therapy-naïve patients and those with inadequate follow-up data were excluded. The primary endpoint was the incidence of cardiotoxicity according to the 2022 European Society of Cardiology guidelines on cardio-oncology. Overall survival was assessed as a secondary endpoint.

Results: Of 353 screened patients, 136 were included (mean age 61.4 years old, 63.2% male). Over a follow-up of 12 [5-21] months (median [Q1-Q3]), 66 (48.5%) patients experienced one or more cardiovascular events including 50 (36.8%) cases of cancer therapy-related cardiac dysfunctions, 16 (11.8%) cases of arrhythmia, 14 (10.3%) cases of vascular toxicity cases and 2 (1.5%) cases of myocarditis. Overall death was recorded in 22 (16.2%) patients. Elevated N-terminal pro brain natriuretic peptide (NT-proBNP) at any time during follow-up was associated with an increased risk of cardiovascular events (increased NT-proBNP: 48 (54.5%) versus (v.s.) normal NT-proBNP: 17 (37.8%) patients; p = 0.041). A comparable effect was observed for baseline NT-proBNP prior to initiation of ICI-therapy (p = 0.038). No association was found for elevated cardiac troponin and C-reactive protein. Stratifying by gender revealed that NT-proBNP and CRP were associated with cardiotoxicity solely in male patients (NT-proBNP: 35 (61.4%) male patients; p = 0.005 and CRP: 38 (57.6%) patients; p = 0.027) with no association in female patients. The overall mortality showed no association with NT-proBNP, but elevated CRP at any time during follow-up was associated with increased overall mortality (increased CRP: 21 (20.8%) vs. normal CRP: 1 (2.9%) patients; p = 0.015).

Conclusion: NT-proBNP and CRP may serve as biomarkers for cardiovascular events in patients receiving ICI therapy. Notably, gender-related differences were observed, with a stronger association in male patients. Prospective data are needed to further evaluate these implications.

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