Effects of immune checkpoint inhibitors on heart, an advanced echocardiographic analysis: the IM.IN.HEART study
Authors: Mandoli G E , Spaccaterra L , Pastore M C , Focardi M , Pecere A , Marchese A , Ghionzoli N , Di Giacomo A M , Maio M , Valente S , Cameli M 
Published: January 2025

Abstract

Introduction
In last decades, novelties and advanced therapies allowed an increase in the life expectancy of patients with cancer. Recently, a central role has been determined by oncological immunotherapy, in particular immune checkpoint inhibitors (ICIs). These therapies, although revolutionary, can cause side effects both at the cardiac and extracardiac levels through partially known mechanisms. Unlike standard chemotherapy (such as anthracyclines), for which early diagnosis of cardiac damage using speckle tracking echocardiography (STE) was widely described, the potential cardiotoxic effects of ICIs are still under evaluation.

Purpose
to assess if ICIs could determine abnormalities in standard and advanced echocardiographic parameters, such as Global Longitudinal Strain (GLS) and Peak Atrial Longitudinal Strain (PALS), indicating subclinical cardiac involvement in patients with or without extracardiac adverse events.

Methods
A total of 42 patients with malignant tumors were prospectively recruited before starting immune ICIs treatment. They underwent clinical, biochemical, basic and advanced echocardiographic evaluations at baseline and 6 months post treatment beginning. Echo indices such as left ventricular size and function, left atrial volume, right ventricular size and function, and estimated pulmonary pressures were assessed. GLS was analyzed by layer-specific approach (endocardial, epicardial, and midwall). Adverse events, including cardiac events (myocarditis, pericarditis), all-cause mortality, and extra-cardiac events, were recorded at each follow-up. Patients with pre-existing heart conditions, prior cardiac surgery, or cardiac pacemakers were excluded. Univariate logistic regression analysis was performed to investigate the correlation between changes in GLS and PALS over time and the occurrence of extra-cardiac adverse effects.

Results
The population (mean age 66±14 years, 69% males), mainly consisted of patients with cutaneous melanoma (44%), pleural mesothelioma (22%), and lung adenocarcinoma (12%), who were predominantly treated with Nivolumab, Pembrolizumab, or a combination of both. Recorded adverse events included 1 fatal myocarditis. Extra-cardiac events included: 8 bone marrow toxicities with anemia, thrombocytopenia, and leukopenia (20%), 4 diarrheas (10%), and 3 cutaneous reactions (7%). Additionally, there were 8 all cause deaths (20%). Comparing the GLS at baseline vs follow up, no significant difference in ventricular or atrial strain values was detected, even analyzing different myocardial layers (Table 1). In myocarditis case, all strain values were instead altered before EF drop. Patients with extracardiac events did not experience a reduction in any strain parameters compared to well-tolerated therapies.

Conclusions
In our preliminary population, ICIs seemed not to reduce longitudinal left heart function, even in case of extracardiac adverse manifestations which are common with the use of these drugs.