Clinical and Diagnostic Significance of Endothelial Dysfunction and Myocardial Contractility in Patients With Acute Myeloid Leukemia
Clinical and Diagnostic Significance of Endothelial Dysfunction and Myocardial Contractility in Patients With Acute Myeloid Leukemia
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.
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.
It is believed that AML affects an average of 3-5 people per 100,000 people per year. At the same time, the incidence increases sharply at the age of over 60 years and amounts to 12-13 cases per 100 thousand of the population in people over the age of 80 years. The median age of this disease is 65 years. With a population of 140 million inhabitants in Russia, the estimated incidence rate (according to European and American researchers) should be about 5 thousand cases.
Anthracycline antibiotics have been an integral part of the treatment of acute myeloid leukemia since the 1970s. Anthracycline is usually given for 3 days (eg, daunorubicin 45-90 mg/m 2 daily, idarubicin 12 mg/m 2 daily) in combination with cytarabine (100-200 mg/m 2 daily) continuously for 7 days ) ("7+3" mode). Anthracyclines block the synthesis of DNA and RNA by inhibiting the enzyme topoisomerase IIβ and mitochondrial topoisomerase I. The subsequent disruption of DNA replication and transcription prevents the proliferation of rapidly dividing cells. In addition, anthracyclines damage DNA, proteins, and cell membranes by creating free oxygen radicals.
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. It is believed to be mediated in part by reactive oxygen species generated by anthracycline treatment, which leads to lipid peroxidation and DNA damage in cardiomyocytes. Other putative causes of anthracycline-induced cardiotoxicity include accumulation of cardiotoxic anthracycline metabolites in the heart, disruption of calcium homeostasis, mitochondrial damage, and induction of apoptosis.
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.
Research objectives
Scientific novelty
Practical significance It is planned to develop an algorithm for early detection of endothelial dysfunction and left ventricular myocardial contractility in patients with acute myeloid leukemia during chemotherapy treatment based on a comprehensive assessment using laser Doppler flowmetry, stress echocardiography with the determination of global longitudinal myocardial strain, biochemical markers of endothelial damage and cardiac biomarkers. .
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.
Research hypothesis:
The proposed algorithm for the early detection of cardiovascular complications in patients with acute myeloid leukemia receiving chemotherapy treatment is an effective method for diagnosing cardiovascular complications at subclinical stages for the timely initiation of their therapy.
Study Design In total, it is planned to study 100 patients with acute myeloid leukemia receiving chemotherapy, aged 18 to 65 years, without clinical signs of heart failure, with an LV ejection fraction of more than 50% before the start of polychemotherapy.
The study group will include patients with acute myeloid leukemia receiving chemotherapy, aged 18 to 65 years, without clinical signs of heart failure, with an LV ejection fraction of more than 50% before the start of polychemotherapy, in whom in the course of chemotherapy treatment after the next course of treatment a decrease in global longitudinal strain of 15% or more relative to the initial values will be revealed.
The control group will consist of patients with acute myeloid leukemia receiving chemotherapy, aged 18 to 65 years, without clinical signs of heart failure, with an LV ejection fraction of more than 50% before the start of polychemotherapy, in whom no signs of myocardial disease and endothelial dysfunction will be detected during chemotherapy.
Inclusion Criteria:
Exclusion Criteria:
i.l.davydkin@samsmu.ru89270145544
a.v.antipova@samsmu.ru89228862745