Multimodality imaging for the detection of cardiotoxicity in cancer patients treated with immune checkpoint inhibitors

Introduction Immune checkpoint inhibitors (ICIs) are considered the new frontier of cancer therapy. However, in some cases ICIs may cause cardiotoxicity, mainly myocarditis, with potential life-threatening consequences. Speckle tracking echocardiography (STE) is recommended as a sensitive, quick, available tool to identify chemotherapy-related cardiotoxicity; it is also useful to aid the diagnosis of myocarditis, for which, however, cardiac magnetic resonance (CMR) is the gold standard imaging method. To date, large-scale prospective data on cardiac imaging after ICI are still lacking. Thus, our aim was to assess the diagnostic and prognostic value of STE for ICI-related cardiotoxicity and evaluate the correlation between STE and CMR in cancer patients treated with ICI. Methods In this prospective study, cancer patients referred for cardiologic evaluation before ICIs initiation were enrolled. Patients with known cardiac dysfunction (LV ejection fraction < 40%) were excluded. All patients underwent clinical, biohumoral and echocardiographic evaluation completed by STE at baseline and at approximately 6 months after immunotherapy. Patients with suspect myocarditis underwent CMR. Then, over a longer follow up, the following clinical events were registered by medical electronic records and phone-calls: all-cause or cardiovascular death, acute myocarditis, acute heart failure, pulmonary embolisms, acute coronary syndromes, atrial or ventricular arrhythmias, extra-cardiac toxicity. Results We enrolled 122 patients (65±14 years) referred for ICIs. Over 7±6 months follow up, medium LV GLS values showed a slight reduction after therapy with ICI, although remaining within the normal ranges. Other STE variables did not show significant differences. During 22±17 months follow up, 65 patients developed events: 26 deaths (1 cardiovascular), 5 acute myocarditis, 4 acute heart failure, 4 new-onset atrial fibrillation, 3 myocardial infarction, 2 pulmonary thromboembolism, 27 extra-cardiac toxicity. Among patients who developed ICI-related myocarditis, 4 patients showed a significant reduction of GLS with a regional distribution similar to with regional myocardial injury at CMR, the fifth had a minimal involvement only of the right ventricle, with normal LV GLS. Conclusion Our results suggest that multimodality imaging combining different techniques, may optimize the subclinical diagnosis of cardiotoxicity and the overall management of cancer patients undergoing ICIs.