Association of Ultrastructural Characteristics of Mitochondria in Cardiomyocytes and Signs of Mitochondrial Dysfunction With the Clinical Course and Outcomes of Heart Failure
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 45
- 试验地点
- 1
- 主要终点
- Combined primary endpoint (percentage)
研究概览
简要总结
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.
详细描述
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 results of the study will be obtained by solving the following tasks:
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Prospective
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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
结局指标
主要结局
Combined primary endpoint (percentage)
时间窗: 12 months
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.
次要结局
- Hospital stay (days)(30 days)
- Postoperative complications during hospitalization (percentage)(30 days)
- Incidence of patients with HF worsening (percentage)(12 months)
研究者
Elena A. Kuzheleva
Senior Researcher
Tomsk National Research Medical Center of the Russian Academy of Sciences