In Vivo Quantitative Mapping of Mitochondrial Cardiac Membrane Potential in Heart Failure

In Vivo Quantitative Mapping of Mitochondrial Cardiac Membrane Potential in Heart Failure

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.

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.

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