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This project is an observational study in patients with heart failure with preserved ejection fraction (HFpEF) who are candidates for treatment with weight loss medication to manage obesity or diabetes as part of their standard clinical care. This study will include multiple experimental visits before and after treatment (minimum 7 percent weight loss, between 9-12 months) to understand how increased adiposity and inflammation effects skeletal muscle and cardiovascular health and function and to examine the effect of medically directed weight loss on skeletal muscle health and exercise tolerance.
The objective of this study is to
Hypotheses
Objective one will also include a cross-sectional comparison between HFpEF patients before treatment and non-HFpEF controls matched for age and hypertension
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| HFpEF and Obesity Group | Patients with HFpEF (heart failure with preserved ejection fraction) and diabetes will undergo standard of care treatment using the most appropriate second-generation anti-diabetic drug that induces clinically significant weight loss after completing baseline (pre) testing. |
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| Control Group (Non-HFpEF and Obesity) | Controls matched for age and hypertension |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Weight loss SOC Treatment with second generation anti-diabetic medications | Drug | To determine the best incretin-based drug for the treatment [done as part of regular standard of care (SOC) treatment], participants will go to UTSW weight wellness clinic and undergo a comprehensive history and physical exam to evaluate their overall health. This information is used to create an individualized approach to the participants weight loss regimen. As part of the regimen, participants will receive guidance on initiating lifestyle modifications including diet and exercise and may be referred to a clinical psychologist for evaluation and management of factors like stress, anxiety and depression, and exercise which may influence their health behaviors and body weight. |
| Measure | Description | Time Frame |
|---|---|---|
| Peak muscle perfusion during exercise | Peak muscle perfusion (Aβ) during exercise will be assessed by Contrast enhanced ultrasound (CEU) | Pre intervention (Day 1) |
| Peak muscle perfusion during exercise | Peak muscle perfusion (Aβ) during exercise will be assessed by Contrast enhanced ultrasound (CEU) | Post intervention (Post Day 1) |
| Single cell RNA sequencing of skeletal muscle | Skeletal muscle biopsies will be taken from the vastus lateralis using the modified Bergstrom technique and immediately prepared for single cell RNA sequencing. Samples will be digested, filtered, washed and resuspended in freezing media and checked for concentration and viability before single cell RNA sequencing is performed | Pre intervention (Day 2) |
| Single cell RNA sequencing of skeletal muscle | Skeletal muscle biopsies will be taken from the vastus lateralis using the modified Bergstrom technique and immediately prepared for single cell RNA sequencing. Samples will be digested, filtered, washed and resuspended in freezing media and checked for concentration and viability before single cell RNA sequencing is performed | Post intervention (Day 2) |
| Muscle to fat ratio of leg | MRI of the leg will be performed to acquire clear visualization of fasciae separating different muscle groups and thus allowing for quantification of intermuscular fat (muscle:fat ratio) | Pre intervention (Day 3) |
| Peak change in microvascular perfusion from rest to exercise | MRI of the leg will be performed utilizing the PIVOT sequence which will measure global and regional perfusion of blood to the muscles in the lower leg at rest and during exercise. the peak change will be reported as the change from baseline to peak exercise |
| Measure | Description | Time Frame |
|---|---|---|
| Vascular function - endothelium dependent vasodilation | A small ultrasound probe will be placed over the brachial artery and a small blood pressure cuff will be positioned on the lower arm, just below the elbow. Images of the vessel will be continuously recorded for 1 min (baseline) before the cuff is inflated to a high pressure (220mmHg) for 5minutes and immediately after the cuff is deflated for 3 minutes. The change in brachial artery diameter following deflation of cuff from baseline will represent a marker of vascular function |
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Inclusion Criteria:
Group 1: Patients with HFpEF
Group 2: Non-HFpEF controls
Exclusion Criteria:
Group 1
Group 2
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Group 1: Patients with HFpEF
- UTSW HFpEF clinic: lead by Dr. Ambarish Pandey
Group 2: non-HFpEF controls
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| Name | Affiliation | Role |
|---|---|---|
| Christopher M Hearon Jr, PhD | University of Texas Southwestern Medical Center | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of Texas Southwestern Medical Center | Dallas | Texas | 75390 | United States |
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| ID | Term |
|---|---|
| D015431 | Weight Loss |
| D009765 | Obesity |
| D007249 | Inflammation |
| ID | Term |
|---|---|
| D001836 | Body Weight Changes |
| D001835 | Body Weight |
| D012816 | Signs and Symptoms |
| D013568 | Pathological Conditions, Signs and Symptoms |
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| Pre intervention (Day 3) |
| Muscle to fat ratio of leg | MRI of the leg will be performed utilizing the PIVOT sequence which will measure the change in perfusion of blood to the muscles in the lower leg from rest to during exercise | Post intervention (Day 3) |
| Peak change in microvascular perfusion from rest to exercise | MRI of the leg will be performed utilizing the PIVOT sequence which will measure global and regional perfusion of blood to the muscles in the lower leg at rest and during exercise. the peak change will be reported as the change from baseline to peak exercise | Post intervention (Day 3) |
| Pre intervention (Day1) |
| Vascular function - endothelium dependent vasodilation | A small ultrasound probe will be placed over the brachial artery and a small blood pressure cuff will be positioned on the lower arm, just below the elbow. Images of the vessel will be continuously recorded for 1 min (baseline) before the cuff is inflated to a high pressure (220mmHg) for 5minutes and immediately after the cuff is deflated for 3 minutes. The change in brachial artery diameter following deflation of cuff from baseline will represent a marker of vascular function | Post intervention (Day 1) |
| Blood volume measurement | The carbon monoxide rebreathe technique will be performed to measure blood volume | Pre intervention (Day1) |
| Blood volume measurement | The carbon monoxide rebreathe technique will be performed to measure blood volume | Post intervention (Day 1) |
| 2min walk endurance test | Participants will be asked to walk on a flat surface back and forth between 2 cones for 2minutes. the total distance covered (in meters) during the 2-minutes will be recorded as a marker of endurance | Pre intervention (Day 2) |
| Hand grip strength | Participants will squeeze a handheld dynamometer as hard as they can to measure handgrip strength (in kg). This will be performed on both hands | Pre intervention (Day 2) |
| 2min walk endurance test | Participants will be asked to walk on a flat surface back and forth between 2 cones for 2minutes. the total distance covered (in meters) during the 2-minutes will be recorded as a marker of endurance | Post intervention (Day2) |
| Hand grip strength | Participants will squeeze a handheld dynamometer as hard as they can to measure handgrip strength (in kg). This will be performed on both hands | Post intervention (Day2) |
| Body composition | measured using dual xray absorptiometry (DEXA) to get lean mass, muscle mass, body fat percentage | Pre intervention (Day 0) |
| Body composition | measured using dual xray absorptiometry (DEXA) to get lean mass, muscle mass, body fat percentage | Post intervention (Day 1) |
| Apnea hypopnea index | Participants will be given an at home sleep apnea test that is incorporated into a wrist-based wearable that enables non-invasive tracking of sleep apnea burden. Sleep apnea will be determined from the apnea hypopnea index measured by the device. Apnea hypopnea index will be calculated as the average number of apneas or hypopneas that occurs per hour of sleep | Pre intervention (Day 2) |
| Apnea hypopnea index | Participants will be given an at home sleep apnea test that is incorporated into a wrist-based wearable that enables non-invasive tracking of sleep apnea burden. Sleep apnea will be determined from the apnea hypopnea index measured by the device. Apnea hypopnea index will be calculated as the average number of apneas or hypopneas that occurs per hour of sleep | Post intervention (Day 2) |
| D050177 | Overweight |
| D044343 | Overnutrition |
| D009748 | Nutrition Disorders |
| D009750 | Nutritional and Metabolic Diseases |
| D010335 | Pathologic Processes |