The prognostic role of pre-treatment global longitudinal strain in patients treated with Immune Checkpoint Inhibitors

Background: Immune checkpoint inhibitors (ICIs) have revolutionized cancer treatment outcomes. However, their use may lead to life-threatening cardiovascular (CV) events, which may necessitate the cessation of life-saving therapy. Left ventricular Global longitudinal strain (LVGLS) is the standard for detecting early myocardial damage in cardiotoxic therapies, however, its role in predicting CV events in patients treated with ICIs has not been assessed.

Objectives: Our study aimed to evaluate the prognostic value of pre-treatment LVGLS in patients treated with ICIs.

Methods: Retrospective single-center cohort of patients treated with ICIs therapy who performed pre-treatment LVGLS assessment. Reduced LVGLS was defined as LVGLS<16%. The endpoints included composite CV events (myocarditis, ACS, HF, and arrhythmias), all-cause mortality, and progression-free survival (PFS).

Results: From 2015 to 2021, 183 patients were included in our cohort. Thirty-eight (21%) patients were included in the Reduced LVGLS group, with a mean LVGLS of 13.2±2.1%, compared to a mean LVGLS of 19.2±2.1% in the Preserved LVGLS group, p<0.001. During a median follow-up of 48 months [IQR: 34-61], 23 (13%) patients developed CV events: 2 (1%) myocarditis, 7 (4%) ACS, 8 (4%) HF, and 12 (7%) arrhythmias. The incidence of CV events was significantly higher in the Reduced LVGLS group (29% vs. 8%, p=0.002), primarily driven by a higher rate of HF exacerbation (13% vs. 2%, p=0.011). Multivariate Cox regression analysis, which included age and baseline IHD and HF, identified pre-treatment Reduced LVGLS as a significant predictor for CV events (adjusted HR=3.27 (95% CI 1.4-7.6), p=0.006) (Figure 1). There were no significant differences between the groups regarding all-cause mortality (p=0.523) and PFS (p=0.793).

Conclusions: Pre-treatment Reduced LVGLS emerged as a strong independent predictor of CV events, suggesting a potential role in risk stratification for adverse CV outcomes.