Effect of Gastric Bypass-induced Weight Loss on Myocardial Structure, Function and Metabolism
Condition: Obesity; Gastric Bypass
MeSH terms: Weight Loss
Study type: Observational

Summary: 
      Obesity affects more than 43 million Americans and is associated with an increased incidence
      of heart failure, sudden death, and cardiovascular death. We have shown that increasing
      obesity is independently associated with potentially detrimental LV structural and
      functional, and metabolic changes. Thus in order to increase our understanding of the effect
      of obesity on the heart, we wish to study the effect of significant weight loss on these
      parameters.
    

Detailed description: 
      Thirty obese patients who weigh <350#, the weight limit of the PET table, who are to undergo
      gastric bypass will be enrolled in this study. Written, informed consent approved by the
      Institutional Review Board of Washington University School of Medicine will be obtained from
      each subject before his/her participation in this study. Subjects will be compensated for
      their time. Subjects will undergo Medical Screening (Visit 1) consisting of a comprehensive
      medical evaluation: a history (questionnaire), physical examination, EKG, blood chemistries,
      kidney function, complete blood count, lipid profiles and pregnancy tests for women of
      childbearing age. Subjects who weigh < 300# will have fat-free mass (body composition)
      determined by using a machine called DEXA. Measurement of Insulin Resistance (Visit 2):
      Subjects will undergo a hyperinsulinemic/euglycemic clamp and nonradiolabeled glucose
      infusion in order to define their level of insulin resistance and total body glucose
      turnover. This study will be performed in the GCRC.

      Measurement of Myocardial Metabolism, Efficiency, Structure, and Function Measures and Total
      Body Fatty Acid Metabolism (Visit 3): Subjects will be admitted to the GCRC the evening
      before the PET imaging and at 6 pm will receive a standard meal. The next morning an 18-gauge
      intravenous catheter will be inserted into your arm vein. A catheter (small tube) will also
      be placed in the radial artery for the total body fat metabolism measurements & for blood
      pressure monitoring. If the subject wishes it, they may have a Foley placed for urination
      during the PET scan studies. Myocardial PET imaging. Studies will be performed during fasting
      conditions at 8 am and ending at 1:00 pm. Each subject will be positioned within the scanner,
      and a 2-min data collection will be acquired to verify proper positioning before a 5-min.
      scan will be performed for generation of attenuation correction factors. Heart blood flow,
      oxygen consumption, and measures of fat metabolism will be obtained using PET imaging after
      the sequential injections of radiolabeled tracers as reported previously by our group. Blood
      pressure and heart rate will be monitored continuously and recorded throughout the image
      acquisition. During the scans, 5 blood samples (0, 2, 10, 20,& 30 min) will be obtained for
      measurement of hormones, heart fuels (e.g. fats, lactate) and carbon dioxide levels.

      Anonymous Genetic Tissue and Data Sampling: Draw and store 1 tablespoon of subject's blood,
      for a period of up to 10 years, to be used in future studies for screening for differences in
      genes related to heart membrane proteins or heart energy metabolism (including but not
      limited to genes known as KV1.5, KV2.1, PPAR, FATP, ACS, PGC-1). Echocardiography:
      Immediately following the PET imaging for oxygen consumption determination, subjects will
      undergo a complete 2D-, 3D-, and Doppler echocardiographic examination. Optison or Definity,
      depending on availability, clinically used intravenous contrast agents may be administered to
      aid with the acquisition of the ultrasound images. Total body fatty acid metabolism
      measurements: Simultaneous with the PET imaging, the subjects will undergo an infusion of a
      tracer amount of nonradioactive fat for measurement of total body fat metabolism. Blood
      samples will be drawn at predetermined times for this measurement.

      3 Months s/p Gastric Bypass Surgery (Visit 4). Blood sampling

      1 Year s/p Gastric bypass Measurement of Body Composition, Blood Chemistries, Lipid Levels,
      and Insulin Resistance (Visits 5 and 6). After the subjects have undergone gastric bypass for
      clinical reasons and are weight stable for 2 weeks (after approximately 1 year post-gastric
      bypass).
    

Observational model: Case-Crossover
Time perspective: Prospective
Sampling method: Non-Probability Sample
Study population: 
        Patients who are to undergo gastric bypass surgery
      
Biospecimen description: 
      2 tubes of blood (1 tablespoon total) will be collected (with permission), tested and stored
      for a length of time
    
Keywords: gastric bypass; obesity