# Effect of Immune Checkpoint Inhibitor Therapy on Biventricular and Biatrial Mechanics in Patients with Advanced Cancer: A Short-Term Follow-Up Study

## TL;DR

This study shows that immune checkpoint inhibitors can cause early heart damage in cancer patients, detectable only with advanced imaging techniques.

## Contribution

The study is the first to comprehensively assess biventricular and biatrial mechanics using STE in ICI-treated patients over a short-term follow-up.

## Key findings

- 85.7% of patients showed subclinical left ventricular dysfunction after 3 months of ICI therapy.
- Both left and right atrial strain parameters declined significantly despite stable conventional echocardiographic measures.
- Baseline LV-GLS independently predicted adverse clinical events and mortality in ICI-treated patients.

## Abstract

Background: Immune checkpoint inhibitors (ICIs) improve cancer outcomes but may cause cardiovascular toxicity, including early subclinical myocardial injury. Conventional echocardiography has limited sensitivity, whereas speckle-tracking echocardiography (STE) allows for early detection of myocardial deformation. Data on short-term ICI-related effects on biventricular mechanics are limited, and atrial function remains poorly characterized. This study evaluated the early impact of ICI therapy on biventricular and biatrial mechanics using STE in patients with advanced cancer. Methods: In this prospective, single-center study, 28 consecutive patients with advanced cancer undergoing ICI therapy were followed for 3 months. Clinical, laboratory, electrocardiographic, and echocardiographic assessments were performed at baseline, 1 month, and 3 months. STE was used to assess left ventricular global longitudinal strain (LV-GLS) and circumferential strain; right ventricular GLS (RV-GLS); and left and right atrial reservoir, conduit, and contractile strain parameters. Subclinical LV dysfunction was defined as a relative LV-GLS reduction >15%. Logistic and Cox regression analyses identified predictors of strain impairment and adverse clinical events. Results: Conventional echocardiographic parameters, including left ventricular ejection fraction, remained stable. In contrast, LV-GLS declined progressively from 20.7 ± 2.1% to 17.6 ± 2.7% at 3 months (p = 0.002), with subclinical LV dysfunction observed in 85.7% of patients. RV-GLS also deteriorated despite preserved TAPSE. Both left and right atrial strain and strain-rate parameters showed an early and marked decline, accompanied by increased left atrial stiffness despite unchanged atrial volumes. Older age and higher neutrophil-to-lymphocyte ratio (NLR) were associated with LV-GLS impairment. Over a mean follow-up of 5.4 ± 3 months, baseline LV-GLS independently predicted adverse clinical events and mortality. Optimal cut-off values were 67 years for age, 4 for NLR, and 19.5% for LV-GLS. Conclusions: Short-term ICI therapy is associated with early, diffuse subclinical myocardial dysfunction involving both ventricles and atria, detectable only by STE. Comprehensive biventricular and biatrial strain assessment may enhance early cardio-oncology surveillance and risk stratification in ICI-treated patients.