Changes and prognostic relationships of markers of cardiotoxicity, endothelial dysfunction, inflammation, and left ventricular diastolic remodeling in patients with lymphomas over long-term monitoring

Aim. To study the profile and long-term changes of recommended markers of cardiotoxicity (high-sensitivity troponin I (hs-TnI), N-terminal pro-brain natriuretic peptide (NT-proBNP)), markers of endothelial dysfunction (endothelin-1 (ET-1)), systemic inflammation (C-reactive protein (CRP), interleukin-6 (IL-6)) and left ventri­cular (LV) structural and functional characteristics in patients with lymphomas 12 months after the start of multiagent chemotherapy, as well as to evaluate the relationship between the obtained data.

Material and methods. The study included patients with newly diagnosed lymphomas (n=30) as follows: 18 men (60%); mean age — 52 [36; 64] years. Hodgkin lymphoma was diagnosed in 8 patients (26,7%), non-Hodgkin lymphomas — in 22 (73,3%). All patients underwent an assessment of laboratory markers (hs-TnI, NT-proBNP, ET-1, CRP, IL-6) and LV structural and functional parameters using speckle tracking echocardiography at baseline and 12 months after the start of treatment.

Results. After 12 months from the start of chemotherapy, no significant changes in the levels of hs-TnI and NT-proBNP were noted. A significant decrease in the le­vels of CRP and IL-6 was observed as follows: from 5,94 [2,98; 34,00] mg/L to 1,31 [0,85; 5,98] mg/L (p=0,002) and from 12,20 [9,95; 12,75] pg/ml to 5,87 [4,7; 7,04] pg/ml (p=0,05), respectively. A significant increase in the median ET-1 level was also noted as follows: 3,46 [2,39; 4,12] ng/ml initially and 11,26 [7,02; 15,5] ng/ml after 12 months (p<0,001). According to echocardiography data, reliable chan­ges of the parameters of LV diastolic function were revealed: a decrease in E/A (p<0,001), an increase in E/e’ (p<0,001), an increase in isovolumic relaxation time (p<0,001) and left atrial volume index (LAVI) (p<0,001). A moderate correlation was found between the ET-1 level and the LAVI (r=0,5; p=0,031) and E/A (r=0,6; p=0,02) values. ROC curve analysis demonstrated the significance of the baseline ET-1 level as a predictor of a E/A decrease (AUC — 0,827±0,096; 95% CI: 0,638-1,000) and LV global longitudinal strain (AUC — 0,747±0,094; 95% CI: 0,563-0,932) after 12-month follow-up.

Conclusion. The obtained data suggest the development of diastolic dysfunction (DD) during the first year after the initiation of chemotherapy in patients with lymphomas. The identified relationship between ET-1 levels and diastolic dysfunction parameters allows us to consider ET-1 as a potential predictor of LV DD in these patients, necessitating their monitoring before and long-term after chemotherapy. In the context of the search for the most effective methods for preventing and predicting cardiovascular toxicity after antitumor therapy, it seems appropriate to further study the relationship between endothelial dysfunction, diastolic dysfunction, heart failure with preserved ejection fraction, and other long-term cardiovascular events in cancer patients after treatment.

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