Ultrastructural Characteristics of Mitochondria in Cardiomyocytes in Heart Failure

NCT05770349 | Recruiting

• 1 other identifier: 23-75-00009
• Study Type: observational
• Target: 45
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Heart Failure; Coronary Artery Disease

Keywords

Chronic heart failure; Mitochondrial function; Mitochondrial DNA; Electron microscopy; SPECT; Cytochrome C; CABG

Outcome Measures

Primary Outcomes (1)

• 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.

  12 months

Secondary Outcomes (3)

• Hospital stay (days)

  30 days

• Postoperative complications during hospitalization (percentage)

  30 days

• Incidence of patients with HF worsening (percentage)

  12 months

Interventions

coronary artery bypass grafting PROCEDURE

Coronary artery bypass grafting

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

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

You may qualify if:

• 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

You may not qualify if:

• 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);
• Severe renal dysfunction (GFR \<30 ml/min/1.73 m2);
• Infiltrative heart diseases (sarcoidosis, amyloidosis, accumulation diseases);
• Autoimmune diseases;
• Acute infectious and exacerbations of chronic somatic diseases
• Type 1 or type 2 diabetes mellitus
• Contraindications to myocardial scintigraphy, cardiopulmonary stress test
• Impossibility of prescribing optimal drug therapy after cardiac surgery

Sponsors & Collaborators

• Russian Science Foundation: collaborator
• Tomsk National Research Medical Center of the Russian Academy of Sciences: lead

Study Sites (1)

Tomsk National Research Medical Center, Russian Academy of Sciences

Tomsk, 634050, Russia

RECRUITING

Related Publications (7)

• Garganeeva A.A., Kuzheleva E.A., Tukish O.V., Vitt K.N., Andreev S.L., Muslimova E.F., Korepanov V.A., Afanasiev S.A., Gulya M.O., Syromyatnikova E.E., Vladimirova E.A., Stepanov I.V. Possibilities of diagnosis of mitochondrial dysfunction in chronic heart failure. Siberian Journal of Clinical and Experimental Medicine. 2024;39(3):51-57. https://doi.org/10.29001/2073-8552- 2024-39-3-51-57.

  BACKGROUND

• Muslimova E.F., Kuzheleva E.A., Garganeeva A.A., Afanasiev S.A. Association of mitochondrial DNA C7028T, G3010A, G9055A polymorphisms and the severity of chronic heart failure of ischemic genesis. Siberian Journal of Clinical and Experimental Medicine. 2025;40(4):123-130. https://doi.org/10.29001/2073-8552-2025-40-4-123-130

  BACKGROUND

• Garganeeva AA, Korepanov VA, Kuzheleva EA, Tukish OV, Vitt KN, Muslimova EF, Afanasiev SA. Chronic heart failure with reduced and mildly reduced left ventricle ejection fraction: relationship between mitochondrial respiratory dysfunction of peripheral blood mononuclear cells and iron deficiency. J Geriatr Cardiol. 2025 Sep 28;22(9):812-817. doi: 10.26599/1671-5411.2025.09.004.

  PMID: 41143166 BACKGROUND

• Garganeeva AA, Kuzheleva EA, Kazakov EP, Syromyatnikova EE, Tukish OV, Kireev II. Association of Cardiomyocyte Mitochondrial Ultrastructure Features with the Severity of Clinical Manifestations in Heart Failure. Kardiologiia. 2026 Jan 14;65(12):13-19. doi: 10.18087/cardio.2025.12.n3062. English, Russian.

  PMID: 41531353 BACKGROUND

• Kuzheleva EA, Garganeeva AA, Tukish OV, Vitt KN, Andreev SL, Syromyatnikova EE, Vladimirova EA. Total Area of Interfibrillar Mitochondria in the Right Atrial Appendage Cardiomyocytes as an Index of the Functional State of the Cardiovascular System in Chronic Heart Failure. Bull Exp Biol Med. 2025 Feb;178(4):486-490. doi: 10.1007/s10517-025-06361-7. Epub 2025 Mar 26.

  PMID: 40138111 BACKGROUND

• Garganeeva A.A., Tukish O.V., Kuzheleva E.A., Gulya M.O., Muslimova E.F., Zhargasova V.A., Popov S.V. Heart failure and mitochondrial dysfunction: research methods in experiment and clinical practice. Acta biomedica scientifica. 2025; 10(1): 103-114. doi: 10.29413/ABS.2025-10.1.11

  BACKGROUND

• Garganeeva AA, Kuzheleva EA, Tukish OV, Vitt KN, Kondratiev MY, Syromyatnikova EE, Andreev SL, Arsenieva YA, Korepanov VA, Afanasiev SA. Acute Decompensated Heart Failure: Structural and Functional Changes in Mitochondria. Kardiologiia. 2024 Dec 24;64(12):12-18. doi: 10.18087/cardio.2024.12.n2737. English, Russian.

  PMID: 39784128 BACKGROUND

Biospecimen

Retention: SAMPLES WITHOUT DNA

fixed tissue, plasma

MeSH Terms

Conditions

Heart Failure; Coronary Artery Disease

Interventions

Coronary Artery Bypass

Condition Hierarchy (Ancestors)

Heart Diseases; Cardiovascular Diseases; Coronary Disease; Myocardial Ischemia; Arteriosclerosis; Arterial Occlusive Diseases; Vascular Diseases

Intervention Hierarchy (Ancestors)

Myocardial Revascularization; Cardiac Surgical Procedures; Cardiovascular Surgical Procedures; Surgical Procedures, Operative; Vascular Grafting; Vascular Surgical Procedures; Thoracic Surgical Procedures

Study Officials

• Alla A Garganeeva, Ph.D.

  Cardiology Research Institute, Tomsk National Research Medical Center, Russian Academy of Sciences

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Elena A Kuzheleva, Ph.D.

CONTACT

+79234010502; kea@cardio-tomsk.ru

Olga V Tukish, Ph.D.

CONTACT

+79069476343; olgatukish@yandex.ru

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Senior Researcher

Study Record Dates

• First Submitted: February 21, 2023
• First Posted: March 15, 2023
• Study Start: March 31, 2023
• Primary Completion (Estimated): November 1, 2026
• Study Completion (Estimated): November 1, 2027
• Last Updated: April 2, 2026

Record last verified: 2026-03

Locations

RU (1)