Cardiovascular Monitoring of Cancer Patients Undergoing Immune Checkpoint Inhibitor Therapy: Preliminary Results from a Prospective Observational Study

Abstract

Abstract Background: the whole spectrum of Immune Checkpoint Inhibitors (ICI) associated cardiovascular immune related adverse events is not fully understood. Only last years it became clear that ICI may cause not only inflammatory cardiovascular diseases. And recent prospective studies have shown subclinical left ventricular disfunction progression in patients treated with ICI but results are bit discordant. Also, specific risk factors of ICI related cardiovascular adverse events didn’t clear yet. Methods: single canter prospective observational study enrolled sixty patients with cancer and indications for ICI. All patients underwent cardiovascular examination before antitumor therapy (n=60), as well as at 3 months (n=34) and 9 months (n=15) following its initiation. The standard examination protocol included evaluation of laboratory parameters, echocardiographic assessment (incl. left ventricular deformation characteristics), Holter monitoring, carotid ultrasound. Results: no statistically significant changes were observed in serum creatinine, C-reactive protein, troponin I, NT-proBNP, and thyroid-stimulating hormone. At the 3-month follow-up, left ventricular (LV) end-systolic volume (ESV) increased from 38±12 ml to 41±11 ml (p=0.026), while LV ejection fraction (EF) decreased from 64% [61;66] to 62% [58;66] (p=0.043). After 9 months patients displayed a continued increase in LV ESV from 35±10 ml to 40±9 ml (p=0.044) and a decrease in LV EF from 64±4% to 60±6% (p=0.012). Additionally, there were observed increases in the diameter of the aortic sinuses of Valsalva (p=0.012), ascending aorta (p=0.046), left atrium (p=0.013), and right ventricle (p=0.011). There was a notable increase in the proportion of patients with atherosclerotic lesions in the carotid arteries, rising from 44% to 60% over the 3-month period (p=0.046). Throughout the follow-up period, novel cardiovascular events occurred in 23.3% of patients (n=14) and included asymptomatic decrease in LV EF and GLS, meeting the established criteria for cardiotoxicity. According to univariate Cox regression analysis, several independent predictors of new CVEs were identified included creatinine, left ventricular Tei index, initial NT-proBNP exceeding 500 pg/ml, TSH concentration, and treatment with anti-PD-L1 immune checkpoint inhibitor. Conclusion: we reveled the high incidence of novel cardiovascular events, presence of subclinical changes of echocardiography parameters, atherosclerosis progression. Also, we defined predictors of ICI related cardiovascular adverse events.