Search for cardiotoxicity predictors of immune checkpoint inhibitors: results of a prospective study

Aim. To assess the incidence of cardiovascular complications associated with immune checkpoint inhibitor (ICI) therapy and identify potential predictors.

Material and methods. The study included 82 patients receiving anticancer treatment with ICIs. Patients were examined before initiation of anticancer therapy (point 0), and at 3 (point 1), and 9 (point 2) months after initiation. The total follow-up period was 12 months. Laboratory parameters, including troponin I, N-terminal pro-brain natriuretic peptide, and markers of atherosclerosis progression (oxidized low-density lipoprotein and heat shock protein), were assessed at all points. All patients underwent echocardiography to assess left ventricular (LV) myocardial strain parameters, carotid ultrasound, and 24-hour electrocardiogram monitoring.

Results. Overall 12-month survival was 51% [40; 64], with no differences between patients with and without underlying cardiovascular disease (46% vs 58%; p=0,405). Clinically insignificant increases in ascending aorta diameter (p=0,040), left atrial size (p=0,16), left atrial volume (p=0,036), and end-systolic volume (p=0,038) were observed, as well as a decrease in LV ejection fraction (p=0,022). No significant changes in cardiac marker levels were observed during the follow-up period. Moreover, the following were identified as predictors of fatal outcomes: initial increase in troponin I level >3,5×10-3 pg/ml (odds ratio, OR: 2,6, 95% confidence interval: 1,3-5,4, p=0,001) and N-terminal pro-brain natriuretic peptide >134,8 pg/ml (OR: 2,4, 95% confidence interval: 1,1-5,3, p=0,038). A high frequency of cardiovascular events of 18,3% (n=15) was revealed. The main predictors of new non-thromboembolic cardiovascular events were a body mass index <20,5 kg/m2 (hazard ratio (HR): 4,2 [1,1; 17,2], p=0,041) and an echocardiographic LV myocardial performance index >0,5 (HR: 10,7 [1,3; 86,5], p=0,026).

Conclusion. A high incidence of cardiovascular complications with ICI therapy was demonstrated, regardless of underlying cardiac pathology in patients. Data support the use of the echocardiographic LV myocardial performance index and body mass index in the basic risk stratification of cardiovascular complications with ICI.

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