Myocardial Injury Following Immune Checkpoint Inhibitors: An Australian Experience

Abstract

Background: Immune checkpoint inhibitors (ICIs) have revolutionised cancer treatment, becoming a cornerstone therapy for various malignancies. Despite their efficacy, there are concerns about their potential cardiotoxicity, particularly, subclinical myocardial injury. However, there remains a scarcity of local data on the precise incidence of such cardiac complications. This prospective pilot study aims to assess myocardial injury in patients undergoing ICI therapy without known cardiovascular disease, using biochemical and cardiac imaging markers of myocardial injury.

Method: A total of 41 patients (median age 68 years, 63% male) receiving ICI therapy without previous cardiac disease were prospectively enrolled. Serial assessments were conducted at baseline and 6 weeks, including measurement of cardiac troponin I (cTnI), N-terminal pro-brain natriuretic peptide (NT-proBNP), and two-dimensional transthoracic echocardiography with speckle tracking strain. Cardiac magnetic resonance imaging (CMR) was performed at 6 weeks. A control group (n=10, median age 66 years, 50% male) with no ICI treatment with matched oncological profile was established. The primary outcome was the incidence of cTnI increase at 6 weeks, with secondary outcomes including changes in NT-proBNP, left ventricular (LV) ejection fraction, LV global longitudinal strain (LV-GLS), right ventricular free wall systolic strain, myocardial injury on CMR, and major adverse cardiac events.

Results: Median baseline cTnI levels measured 4.0 (interquartile range 3.0-7.0) ng/L, with only one patient (2.7%) demonstrating significant cTnI increase after ICI therapy. Follow-up assessments revealed no significant mean differences in cTnI, NT-proBNP, LV ejection fraction, or right ventricular free wall systolic strain. However, a significant change in LV-GLS was noted in the ICI group (-1.2%, p=0.004) compared with controls (-0.7%, p=0.50, p=0.02). A total of 20 patients (54%) underwent CMR, with 11 (55%) exhibiting abnormalities (T1/T2 mapping and late gadolinium enhancement). Of the nine patients (45%) with increased T1 mapping on CMR, all demonstrated a reduction in LV-GLS between baseline and 6 weeks, with a mean reduction of 5% (3%-12%). Within 1 year, major adverse cardiac events occurred in 17 (45.9%) patients.

Conclusions: Although the occurrence of significant cTnI increase was low, subclinical myocardial injury can be detected through advanced cardiac imaging after ICI initiation. This underscores the importance of conducting larger studies to further elucidate the prevalence, mechanisms, and clinical implications of myocardial injury in patients receiving ICI treatment.

Keywords: Cardiovascular magnetic resonance; Echocardiography; Immune checkpoint inhibitors; Myocardial injury; Troponin I.