Effect of Weight Loss on Myocardial Metabolism and Cardiac Relaxation in Obese Adults

Study Overview
=================
Brief Summary
-----------------
Obesity adversely affects myocardial (muscular heart tissue) metabolism, efficiency, and diastolic function. The objective of this study was to determine if weight loss could improve obesity-related myocardial metabolism and efficiency and if these improvements were directly related to improved diastolic function.

Detailed Description
-----------------
This was a prospective, interventional study in obese adults ages 21 to 50 years of age to determine whether weight loss could improve obesity-related myocardial metabolism and efficiency. Two different mechanisms of weight loss were studied: diet and exercise and gastric bypass surgery. Positron emission tomography (PET) was used to quantitate myocardial oxygen consumption (MVO2) and myocardial fatty acid (FA) metabolism. Echocardiography with tissue Doppler imaging was used to quantify cardiac structure, systolic and diastolic function (left ventricular (LV) relaxation (E') and septal ratio (E/E')).

Official Title
-----------------
Effect of Weight Loss on Myocardial Oxygen Consumption and Left Ventricular Relaxation in Obese Adults

Conditions
-----------------
Obesity

Intervention / Treatment
-----------------
* Behavioral: Diet
* Procedure: Gastric bypass surgery


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Body mass index (BMI) > 30 kg/m^2 Sedentary lifestyle Exclusion Criteria: Body weight >159 kg Insulin-requiring diabetes Heart failure History of coronary artery disease Chest pain Untreated sleep apnea Being an active smoker Pregnant, lactating, or postmenopausal

Ages Eligible for Study
-----------------
Minimum Age: 21 Years
Maximum Age: 50 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Basic Science
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Diet<br>Participants who received counseling and instruction about weight loss through diet and exercise | Behavioral: Diet<br>* Participants attended 20 group behavioral modification sessions led by a behaviorist, a registered dietician, and a physical therapist. The meal plans ranged from 1200 to 1500 kilocalories per day, depending on subject sex and BMI, and were designed to achieve ≤1% body weight loss/week. Participants completed daily food records, and were taught a variety of weight management skills. The exercise component included strength, flexibility, balance, and endurance instruction, gradually increasing to 30 minutes of exercise 5 days/week.<br>|
| Experimental: Gastric bypass surgery<br>Participants who received gastric bypass surgery | Procedure: Gastric bypass surgery<br>* The same surgeon performed all bypass procedures using standard techniques. A small ( 20 ml) proximal gastric pouch was created by stapling the stomach, and a 75-cm Roux-en-Y limb was constructed by transecting the jejunum distal to the ligament of Treitz, and creating a jejunojejunostomy 75 cm distal to the transection.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Total Myocardial Oxygen Consumption (MVO2) | The evening before an imaging study, all participants were given a meal containing 12 kcal/kg adjusted body weight (=ideal body weight + ((actual body weight-ideal body weight) x 0.25)). Participants fasted until their imaging studies were completed. Myocardial oxygen consumption (MVO2) was measured using positron emission tomography (PET) following injection of 1-^11C-acetate. Total MVO2 was calculated by multiplying the MVO2 measure by left ventricular weight. | Measured at baseline, 16 months after gastric bypass surgery-induced weight loss, and 8 months after diet-induced weight loss | 
| Total Myocardial Fatty Acid (FA) Utilization | The evening before an imaging study, all participants were given a meal containing 12 kcal/kg adjusted body weight (=ideal body weight + ((actual body weight-ideal body weight) x 0.25)). Participants fasted until their imaging studies were completed. Myocardial blood flow was measured using positron emission tomography (PET) following injection of ^30O-water. Myocardial fatty acid (FA) utilization was measured using PET after injection of 1-^11C-palmitate. The calculations that describe the relationship between the different measures of myocardial FA metabolism are: FA utilization/gram = blood flow/gram × FA uptake/gram × [average plasma free FA at the time of the 1-11C-palmitate injection]; FA utilization/gram = FA oxidation/gram + esterification/gram. Total fatty acid utilization was calculated by multiplying the fatty acid utilization rate by left ventricular weight. | Measured at baseline, 16 months after gastric bypass surgery-induced weight loss, and 8 months after diet-induced weight loss | 
| Total Myocardial Fatty Acid (FA) Oxidation | The evening before an imaging study, all participants were given a meal containing 12 kcal/kg adjusted body weight (=ideal body weight + ((actual body weight-ideal body weight) x 0.25)). Participants fasted until their imaging studies were completed. Myocardial fatty acid utilization was measured using positron emission tomography (PET) after injecting 1-^11C-palmitate. Total fatty acid oxidation was calculated by multiplying the fatty acid oxidation rate by left ventricular weight. | Measured at baseline, 16 months after gastric bypass surgery-induced weight loss, and 8 months after diet-induced weight loss | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Left Ventricular (LV) Relaxation (E') | Immediately following MVO2 measurement, complete two-dimensional, M-mode, and Doppler echocardiographic studies were performed using second harmonic imaging. Left ventricular relaxation (E') was measured at the lateral annulus. All reported measurements represent the average of three consecutive cardiac cycles. A single investigator blinded to all clinical parameters evaluated all echocardiograms. | Measured at baseline, 16 months after gastric bypass surgery-induced weight loss, and 8 months after diet-induced weight loss | 
| Septal Ratio (E/E') | Immediately following MVO2 measurement, complete two-dimensional, M-mode, and Doppler echocardiographic studies were performed using second harmonic imaging. The early diastolic (E) velocity was measured, left ventricular relaxation (E') was measured at the lateral mitral annulus, and the E/E'(septal) ratio was calculated. All reported measurements represent the average of three consecutive cardiac cycles. A single investigator blinded to all clinical parameters evaluated all echocardiograms. The normal septal ratio from the lateral mitral annulus is <5, a ratio from 5 to 10 is indeterminate, and a ratio of >10 indicates elevated left atrial pressure. | Measured at baseline, 16 months after gastric bypass surgery-induced weight loss, and 8 months after diet-induced weight loss | 
| Left Ventricular (LV) Mass | Immediately following MVO2 measurement, complete two-dimensional, M-mode, and Doppler echocardiographic study were performed using second harmonic imaging. Left ventricular (LV) mass was measured using the area-length method. All reported measurements represent the average of three consecutive cardiac cycles. A single investigator blinded to all clinical parameters evaluated all echocardiograms. | Measured at baseline, 16 months after gastric bypass surgery-induced weight loss, and 8 months after diet-induced weight loss | 
| Mean Heart Rate | Heart rate was measured at scheduled physical examinations. | Measured at baseline, 16 months after gastric bypass surgery-induced weight loss, and 8 months after diet-induced weight loss | 
| Mean Arterial Pressure | Mean arterial pressure was measured at scheduled physical examinations. | Measured at baseline, 16 months after gastric bypass surgery-induced weight loss, and 8 months after diet-induced weight loss | 
| Mean Body Mass Index | Participant weight and height was measured at scheduled physical examinations. Body mass index was calculated as participant body weight in kilograms divided by their height in meters squared. | Measured at baseline, 16 months after gastric bypass surgery-induced weight loss, and 8 months after diet-induced weight loss | 
| Mean Total Serum Cholesterol and Triglycerides | Blood testing was conducted at scheduled times during the study. Serum cholesterol and triglycerides were measured by the enzymatic method (Roche Diagnostics). | Measured at baseline, 16 months after gastric bypass surgery-induced weight loss, and 8 months after diet-induced weight loss | 
| Mean Homeostasis Model Assessment of Insulin Resistance | The homeostasis model assessment of insulin resistance (HOMA) was used to calculate insulin resistance using the first AM, fasting glucose and insulin levels. Plasma insulin levels were measured by radioimmunoassay, and glucose levels were measured by automated hexokinase assay. A HOMA score of <3 represents normal insulin resistance, a score between 3 and 5 moderate insulin resistance, and a score of 5 or higher represents severe insulin resistance. | Measured at baseline, 16 months after gastric bypass surgery-induced weight loss, and 8 months after diet-induced weight loss | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Heart Metabolism, Obesity, Weight loss, Gastric bypass surgery, Diet and exercise