The prognostic value of the NT-proBNP biomarkers and Fas ligand in assessing the risk of cardiotoxicity of anthracycline chemotherapy

A T Teplyakov,K V Kopeva,E V Grakova,S N Shilov,M N Neupokoeva,A A Popova,E N Berezikova

doi:10.15829/1728-8800-2019-1-127-133

Abstract

Aim. To study the mechanisms, features of clinical manifestations and predicting of cardiotoxicity resulting from anthracycline chemotherapy.Material and methods. We examined 176 women with breast cancer who received anthracycline antibiotics as part of polychemotherapeutic (PCT) treatment. Patients were divided into 2 groups: with the development of cardiotoxic remodeling — group 1 (n=52) and with preserved heart function — group 2 (n=124). We conducted echocardiographic (EchoCG) tests before the start, during and after anthracycline chemotherapy. In the serum after the termination of PCT treatment, the concentrations of N-terminal prohormone of brain natriuretic peptide (NT-proBNP) and soluble Fas ligand (sFas-L) were determined.Results. Analysis of EchoCG parameters in patients after 12 months of PCT finish, showed a significant difference in the final systolic and end diastolic sizes, as well as a significant decrease in the left ventricular ejection fraction in group 1 compared with those before the start of treatment. A direct correlation was found between the end-systolic and end-diastolic volumes and inverse correlation between left ventricular ejection fraction and the resulting summary dose of doxorubicin. EchoCG changes in women of group 1 after the first course of PCT treatment were recorded in 49% of cases and 11% of cases — in group 2. The concentrations of sFas-L and NT-proBNP after PCT therapy finish in group 1 were significantly higher compared with group 2. Patients with significantly elevated NT-proBNP levels were had a high risk of heart disease developing during 12 months follow-up. A high concentration of NT-proBNP is a predictor of cardiovascular complications, which is more sensitive than EchoCG.Conclusion. Fas-associated apoptosis plays an important role in the pathogenesis of anthracycline cardiotoxicity. NT-proBNP may be an important biomarker for cardiotoxicity development, which already effective when EchoCG or clinical signs is absent.

Highlights

The prognostic value of the NT-proBNP biomarkers and Fas ligand in assessing the risk of cardiotoxicity of anthracycline chemotherapy
We examined 176 women with breast cancer who received anthracycline antibiotics as part of polychemotherapeutic (PCT) treatment
EchoCG changes in women of group 1 after the first course of PCT treatment were recorded in 49% of cases and 11% of cases — in group 2

Summary

Материал и методы

Обследованы 176 женщин с раком молочной железы, получавших антрациклиновые антибиотики в составе схем ПХТ. После окончания ПХТ пациентки, находящиеся в состоянии ремиссии основного заболевания, были разделены на 2 группы: больные с развитием кардиотоксического ремоделирования — группа 1 (n=52), средний возраст — 46,1±5,1 лет, и женщины с сохраненной функцией сердца — группа 2 (n=124), средний возраст — 45,2±3,8 лет. Всем больным до начала курса химиотерапии, в динамике лечения антрациклинами и после терапии таковыми проводилось исследование ЭхоКГ-показателей. В сыворотке крови исходно и после окончания противоопухолевой ПХТ определяли концентрации предшественника мозгового натрийуретического пептида (NT-proBNP) и индуктора апоптоза — растворимого Fas-лиганда (sFas-L). Участвующие в исследовании, не имели доказанной патологии со стороны сердечно-сосудистой системы, выраженной сопутствующей патологии, сахарного диабета до начала противоопухолевого лечения. Отсутствие кардиологической патологии было подтверждено данными анамнеза, электрокардиографии, ЭхоКГ. В исследование не включали женщин с прогрессировани-

После завершения ПХТ

Findings

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