Ultrastructural Characteristics of Mitochondria in Cardiomyocytes in Heart Failure

Summary

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.

Eligibility

Inclusion Criteria:

1. The presence of HFrEF or HFmrEF (EF of LV \<50%)
2. Obstructive multivessel coronary atherosclerosis as an indication for cardiac surgical correction of coronary blood flow (coronary bypass surgery)
3. Signed informed consent to participate in the study, separate consents for biomaterial sampling and genetic research

Exclusion Criteria:

1. Refusal of revascularization or participation in the study
2. Additional cardiac surgery other than coronary bypass surgery (valves, aneurysm)
3. Oncological diseases in the active stage;
4. The presence of implanted devices (EX, AICD, CT);
5. Severe renal dysfunction (GFR \<30 ml/min/1.73 m2);
6. Infiltrative heart diseases (sarcoidosis, amyloidosis, accumulation diseases);
7. Autoimmune diseases;
8. Acute infectious and exacerbations of chronic somatic diseases
9. Type 1 or type 2 diabetes mellitus
10. Contraindications to myocardial scintigraphy, cardiopulmonary stress test
11. Impossibility of prescribing optimal drug therapy after cardiac surgery

Conditions3

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