Clinical and Diagnostic Significance of Endothelial Dysfunction and Myocardial Contractility in Patients With AML

Summary

Acute myeloid leukemia (AML) is a clonal neoplastic disease of the hematopoietic tissue associated with a mutation in the precursor cell of hematopoiesis, which results in a differentiation block and uncontrolled proliferation of immature myeloid cells.

Anthracycline antibiotics have been an integral part of the treatment of acute myeloid leukemia since the 1970s. However, the clinical usefulness of anthracyclines is limited primarily by the high incidence of cardiotoxicity. According to the European Society of Cardiology guidelines for cardio-oncology, cardiovascular toxicity is defined as any impairment of cardiac function associated with anticancer treatment, as the term encompasses both a wide range of possible clinical manifestations and an etiological relationship with various treatments, including chemotherapy, radiation therapy, immunotherapy and treatment with targeted drugs. Cardiovascular toxicity can be acute, subacute or delayed, manifesting many years after chemotherapy or radiation therapy, involving a number of cardiac structures, which can lead to the development of heart failure, coronary heart disease, valvular heart disease, arrhythmias, including cardiac conduction disorders and diseases of the pericardium.

Anthracycline-induced cardiotoxicity is the negative effect of anthracyclines on normal cardiac activity due to their toxic effects on the heart muscle and the cardiac conduction system. Anthracycline-induced cardiotoxicity manifests as asymptomatic left ventricular dysfunction in 57% of treated patients and restrictive or dilated cardiomyopathy leading to congestive heart failure (CHF) in 16% to 20% of patients. Anthracycline-induced congestive heart failure is often resistant to therapy and has a mortality rate of up to 79%. Thus, there is a need for early detection of cardiovascular dysfunction associated with chemotherapy treatment of acute myeloid leukemia in order to timely prescribe drug therapy.

Purpose of the study To optimize the early detection of endothelial dysfunction and left ventricular myocardial contractility in patients with acute myeloid leukemia during chemotherapy treatment based on a comprehensive assessment of instrumental and laboratory research parameters.

Expected results Based on a comprehensive analysis using laser Doppler flowmetry, stress echocardiography with the determination of global longitudinal strain of the myocardium, biochemical markers of endothelial damage and cardiac biomarkers, a correlation between violations of the contractility of the left ventricular myocardium and violations of the vasoregulatory function of the vascular endothelium will be revealed, which will allow developing an algorithm for early detection of cardiomyopathy and vascular complications in patients with acute myeloid leukemia during chemotherapy treatment.

Conditions

• Acute Myeloid Leukemia, Adult
• Cardiotoxicity
• Endothelial Dysfunction

Interventions

DIAGNOSTIC_TEST

History taking

Careful history taking, including using questionnaires, to identify risk factors for the development of cardiovascular diseases using the SCORE scale.

DIAGNOSTIC_TEST

Anthropometry

Anthropometry: measurement of body weight and height. Calculation of body surface area using the Du Bois formula.

DIAGNOSTIC_TEST

Complete blood count

Before and after each course of chemotherapy: Complete blood count with counting the number of erythrocytes, leukocytes, leukocyte formula, platelets, erythrocyte sedimentation rate.

DIAGNOSTIC_TEST

Biochemical blood test

Before and after each course of chemotherapy: Biochemical blood test with the determination of the amount of total protein, total cholesterol, HDL cholesterol, LDL cholesterol, triglycerides, creatinine, urea, AlAT, AsAT, LDH, glucose, C-reactive protein, troponin T, proBNP.

DIAGNOSTIC_TEST

Coagulogram

Before and after each course of chemotherapy: Coagulogram parameters (fibrinogen, APTT, INR).

DIAGNOSTIC_TEST

Immunoenzymatic analysis of the level of endothelin-1, asymmetric dimethylarginine

Before the start of the treatment and after each course of chemotherapy: Immunoenzymatic analysis of the level of endothelin-1, asymmetric dimethylarginine.

DIAGNOSTIC_TEST

Stress echocardiography with the definition of global longitudinal deformation of the myocardium

Before the start of the treatment and after each course of chemotherapy: Stress echocardiography with the definition of global longitudinal deformation of the myocardium.

DIAGNOSTIC_TEST

Triplex scanning of neck vessels

Before the start of the treatment and after each course of chemotherapy: Triplex scanning of neck vessels.

DIAGNOSTIC_TEST

Electrocardiography

Before and after each course of chemotherapy: Electrocardiography.

DIAGNOSTIC_TEST

Ultrasound of the abdominal cavity (with calculation of the area of the spleen) and lymph nodes

Before the start of the treatment and after each course of chemotherapy: Ultrasound of the abdominal cavity (with calculation of the area of the spleen) and lymph nodes.

DIAGNOSTIC_TEST

Cytogenetic examination of the bone marrow to determine genetic abnormalities.

Before the start of the treatment: Cytogenetic examination of the bone marrow to determine genetic abnormalities.

DIAGNOSTIC_TEST

Cytological examination of bone marrow cells with cytochemical examination

Before the start of the treatment and after each course of chemotherapy: Cytological examination of bone marrow cells with cytochemical examination.

DIAGNOSTIC_TEST

Immunophenotypic examination of the bone marrow by flow cytometry

Before the start of the treatment: Immunophenotypic examination of the bone marrow by flow cytometry.

DIAGNOSTIC_TEST

Determination of the presence of a FLT3 mutation using the PCR Method

Before the start of the treatment: Determination of the presence of a FLT3 mutation using the PCR Method.

DIAGNOSTIC_TEST

laser Doppler flowmetry

Before the start of the treatment and after each course of chemotherapy: Examination of microcirculation by laser Doppler flowmetry using the LAKK-OP apparatus (NPP Lazma, Moscow, 2011) with respiratory and occlusion tests.

Sponsors & Collaborators

• Samara State Medical University

  lead OTHER

Principal Investigators

• Igor Davydkin · Samara State Medical University

Study Design

Allocation

NON_RANDOMIZED

Purpose

DIAGNOSTIC

Masking

SINGLE

Model

PARALLEL

Eligibility

Min Age

18 Years

Max Age

65 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2022-12-01

Primary Completion

2025-01-01

Completion

2025-08-03

Countries

• Russia

Study Locations