According to modern concepts, mitochondrial dysfunction may be the fundamental basis for the development and progression of CHF, including in patients undergoing myocardial revascularization. The processes of mitochondrial fusion, division and mitophagy are aimed at maintaining cellular homeostasis. A change in the balance of these processes can lead to the accumulation of damaged organelles with impaired functions. In patients with CHF, dysfunctional mitochondria are characterized by size dispersion, crist disorganization, and localization changes relative to myofibrils.
At the same time, the topic of the influence of mitochondrial dysfunction on the prognosis and clinical course of CHF remains debatable today. Direct study of the structural and functional features of mitochondria in human cardiomyocytes is an extremely difficult task, and therefore, such studies are carried out extremely rarely and on very limited cohorts. In the planned study, due to the long time of the study material recruitment, the ultrastructure of mitochondria in a large cohort of patients, ranging from 45 to 60 people, will be studied.
The aim of this study is to study the association of mitochondrial dysfunction with the clinical course and outcomes of CHF of ischemic etiology, as well as to assess the degree of compliance of indirect criteria of mitochondrial dysfunction with direct ultrastructural characteristics of mitochondria in cardiomyocytes.
This single-center prospective cohort study will involve 45-60 patients. The patients will have biopsy samples taken from the right auricle, as well as blood collection and preservation and its derivatives. Electron microscopy of myocardial samples will be performed to assess the ultrastructure of mitochondria of cardiomyocytes. The results of a direct study of mitochondria will be compared with indirect signs of mitochondrial dysfunction: the registration of the phenomenon of increased leaching of radiopharmaceuticals from the myocardium, an increase in the number of copies of mitochondrial DNA and the concentration of cytochrome C in the blood, the affiliation of mitochondrial DNA to haplogroup K. The results obtained in each of the research tasks will have high scientific significance and publication potential.
The presence of HFrEF or HFmrEF (EF of LV <50%)
Obstructive multivessel coronary atherosclerosis as an indication for cardiac surgical correction of coronary blood flow (coronary bypass surgery)
Signed informed consent to participate in the study, separate consents for biomaterial sampling and genetic research
Refusal of revascularization or participation in the study
Additional cardiac surgery other than coronary bypass surgery (valves, aneurysm)
Oncological diseases in the active stage;
The presence of implanted devices (EX, AICD, CT);
45-60 patients will be included in the study (15-20 people each - in 2023, 2024 and 2025) who meet the stated inclusion and exclusion criteria. The signing of the informed consent will be carried out before the start of any research procedures, the patient will be explained in detail the protocol of the study and the scope of the diagnostic procedures carried out
Cohort
Prospective
coronary artery bypass grafting
Procedure/SurgeryCoronary artery bypass grafting
Combined primary endpoint (percentage)
Combined primary endpoint is calculated as a percentage (%) of patients with one or several outcomes including: cardiovascular death and/or hospitalization for decompensated HF or the need for parenteral administration of a diuretic and/or acute ischemic events or repeated unplanned revascularization and/or unplanned impalement of cardiac implantable electronic devices.
Hospital stay (days)
Number of days of hospitalization following coronary artery bypass grafting (CABG) surgery.
Postoperative complications during hospitalization (percentage)
Postoperative complications during hospitalization are assessed as percentage of patients with complications after CABG.
Incidence of patients with HF worsening (percentage)
Worsening of heart failure (HF) is assessed based on NYHA class change.
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Tomsk National Research Medical Center of the Russian Academy of Sciences
Lead sponsor
Russian Science Foundation
Collaborator
