Mitochondrial Function
Conditions
Keywords
mitochondrial function, positron emission tomography, heart failure
Brief summary
This research aims to develop a new method to measure how well mitochondria are working using a special imaging technique called PET (positron emission tomography) with a tracer called 18F-TPP+. This tracer helps us visualize and measure mitochondrial function in a non-invasive way.
Detailed description
Our study has three main goals: 1. Measure Mitochondrial Function in Different Groups: The investigators will compare mitochondrial function in three groups: healthy active individuals, sedentary individuals, and heart failure patients. The investigators expect to see higher mitochondrial function in active individuals and lower function in heart failure patients. The investigators will also test the consistency of our measurements. 2. Correlate Mitochondrial Function with Health Indicators: The investigators will see if our mitochondrial function measurements relate to other health markers, such as exercise capacity, heart health, muscle strength, and cognitive function. 3. Improve the Production of the Tracer: The investigators will refine how they make the 18F-TPP+ tracer to make it more efficient and cost-effective for widespread use in research and clinical settings.
Interventions
18F-TPP+ PET/CT imaging
Sponsors
Study design
Eligibility
Inclusion criteria
* Active participants: 1. ≥40 years old 2. LVEF ≥50% 3. Body Mass Index \<35kg/m2 4. NYHA fuctional class I 5. Engaged in aerobic exercise (running cycling or swimming) for ≥3 days per week or 5 hours per week without extensive layoff over the previous 6 months 6. Non-smoker ≥1 year 7. Fasting glycemia \<6.0 mmol/L 8. HbA1c \<5.7% * Sedentary participants: 1. ≥40 years old 2. LVEF ≥50% 3. Body Mass Index \<35kg/m2 4. NYHA fuctional class 5. ≤1 structured physical activity per week 6. Non-smoker ≥1 year 7. Fasting glycemia \<6.0 mmol/L 8. HbA1c \<5.7% * HFpEF participants: 1. Chronic symptomatic HF and LVEF \>40% within 12 months before the screening visit (regardless of the imaging modality) 2. One of the following abnormalities: 1. HF requiring hospitallization and IV diuretics within 12 months of study entry 2. NTproBNP \>150 pg/ml in sinus rhythm 3. NTproBNP \>450 pg/ml in chronic atrial fibrillation
Exclusion criteria
* for all participants : 1. Infiltrative CMP (e.g., cardiac amyloidosis) 2. Hypertrophic CMP 3. Dilated CMP 4. Ischemic CMP with myocardial infarction 5. Other chronic diseases or medications that may interfere with mitochondrial function 6. Primary severe valvular disease 7. Pericardial disease 8. Pacemaker 9. Defibrillator 10. Congenital heart disease 11. History of cardiac transplant 12. BMI \>45 kg/m2 13. High resting blood pressure ≥150/90 mmHg 14. Estimated glomerular filtration rate (eGFR) \<50 mL/min/1.73m2 15. Iodinated contrast allergy 16. Women of child bearing potential 17. Pregnancy 18. Breastfeeding 19. Inability to undergo the imaging logistics 20. Any condition that, in the opinion of the investigator, could compromise the participation in the study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Average difference of membrane potential (ΔΨT) in sedentary adults vs subjects with Heart Failure with Preserved Ejection Fraction (HFpEF) | Up to 3 months | Compare membrane potential (ΔΨT) of patients suffering from Heart Failure with Preserved Ejection Fraction (HFpEF) to healthy sedentary adults matched for age and sex. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Average difference of membrane potential (ΔΨT) in active adults vs healthy sedentary adults | Up to 3 months | Compare membrane potential (ΔΨT) of healthy active adults to healthy sedentary adult matched for age and sex. |
| Correlation coefficients between membrane potential (ΔΨT) and ECV vs VO2max, grip strength, left ventricular mass, NT-pro-BNP, neurocognitive function, and NYHA functional class. | Up to 5 months | Evaluate the correlation between membrane potential (ΔΨT) and ECV with clinical biomarkers of HF including VO2max, grip strength, left ventricular mass, NT-pro-BNP, neurocognitive function, and NYHA functional class. |
| Coefficient of repeatability between membrane potential (ΔΨT) and ECV repeated measurements. | Up to 3 months | Evaluate the repeatability of in vivo measurements of membrane potential (ΔΨT) and ECV. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Correlation between in vivo measurements of membrane potential (ΔΨT) and ECV with metabolites reflecting mitochondrial function. | Up to 3 months | Explore the association between in vivo measurements of membrane potential (ΔΨT) and ECV with metabolites reflecting mitochondrial function. |
Countries
Canada