Association of endothelin-1 levels and left ventricular diastolic function parameters in patients with lymphomas 12 months after polychemotherapy

Long-term follow-up of patients with lymphomas revealed that cardiovascular events, including those related to cardiovascular toxicity (CVT) of antitumor therapy, rank among the leading causes of non-oncological mortality. An in-depth study of CVT pathophysiological mechanisms is fundamental for developing effective approaches for its prevention and monitoring in this cohort of patients.

To assess the potential link between endothelial dysfunction and changes in left ventricular (LV) diastolic function parameters as a potential mechanism for the development of CVT in long-term follow-up of patients with lymphomas undergoing antitumor therapy.

The prospective study included 30 patients newly diagnosed with lymphomas: 18 women (60%); mean age - 52 [36-64] years. Hodgkin lymphoma was diagnosed in 8 (26.7%) patients, non-Hodgkin lymphomas in 22 (73.3%) patients. All patients underwent assessment of serum level of the endothelial dysfunction marker endothelin-1 (ET-1), structural and functional parameters of LV myocardium using speckle-tracking echocardiography at baseline and 12 months after the initiation of polychemotherapy (PCT). Statistical and correlation analyses were performed using SPSS Statistics. The study was approved by our University.

After 12 months, no criteria for CVT as defined by the 2022 ESC Guidelines on cardio-oncology were met: the median values of LV ejection fraction and global longitudinal strain remained within normal values. However, a statistically significant increase in median ET-1 level was observed: 3.46 [2.89-4.02] initially to 11.26 [7.02-15.5] pg/ml after 12 months (p=0.001). Significant changes of LV diastolic function characteristics were also demonstrated: a decrease in E/A, an increase in E/e', prolonged LV isovolumic relaxation time, and an increase in indexed left atrium volume (LAVi). Statistical analysis revealed moderate direct correlations between ET-1 levels and LAVi (r=0.5; p=0.031), as well as between ET-1 levels and E/A (r=0.6; p=0.02).

This study demonstrates that LV diastolic dysfunction may represent a novel manifestation of CVT of antitumor therapy in patients with lymphomas. The findings suggest a potential link between endothelial damage and LV diastolic dysfunction. Further investigation is required to confirm these observations, along with the inclusion of a comprehensive assessment of endothelial damage markers and LV diastolic function parameters into the long-term cardiovascular monitoring for patients after antitumor therapy.