Clinical trial

The Effect of Adiposity on Muscle and Microvascular Function in HFpEF

Invitation only · Not applicable · 1 countries · Registry ID NCT06930495

Invitation onlyNot applicableObservational

What this study is about

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 1. Define the mechanisms by which adiposity impairs exercise hemodynamics, microvascular function, and oxygen transport/utilization in patients with HFpEF. 2. Determine if intensive medically directed weight loss can reduce microvascular inflammation and normalize exercise hemodynamics. 3. Quantify the effect of medically directed weight loss on skeletal muscle function and catabolism. Hypotheses 1. Perfusion of subcutaneous adipose tissue disrupts blood flow distribution and impairs muscle microvascular perfusion and exercise hemodynamics. 2. Extramyocellular muscular lipid deposition and microvascular endothelial inflammation is associated with reduced capillarity and impaired microvascular perfusions, while intramyocellular triglyceride content is associated with poor skeletal muscle oxidative capacity, 3. Intensive weight loss will improve exercise hemodynamics, microvascular perfusion, and reduce muscular inflammation, and resistance training will augment these effects.

A promising-looking record is not the same as confirmed eligibility. The study team must review the full criteria and current recruitment status.

Basic eligibility

Age18 Years to Not listed

SexAll

Healthy volunteersAccepted

ConditionHeart Failure With Preserved Ejection Fraction (HFPEF)

Full registry criteria

Inclusion Criteria: Group 1: Patients with HFpEF * Diagnosis of heart failure or clear heart failure hospitalization * Stable ejection fraction \> 0.50 * Objective evidence of elevated left ventricular filling pressure by one of the following i) pulmonary capillary wedge pressure ≥25 mmHg during supine cardiopulmonary exercise testing or ii) a change in pulmonary capillary wedge pressure of \>15 mmHg during upright exercise * Must be candidates for pharmacological incretin-based directed intensive weight loss therapies as part of their SOC * BMI\>32kg/m2 * ≥45 years old * Incretin naïve for 6 months Group 2: Non-HFpEF controls * Adults who do not have heart failure with preserved ejection fraction * Age ≥ 18 years Exclusion Criteria: Group 1 * Prior history of reduced ejection fraction (\<50%) * Infiltrative cardiomyopathy * NYHA Class IV chronic heart failure * Left bundle branch block * Unstable coronary artery disease * Uncontrolled arrhythmia * CKD 4 or higher * Currently taking incretin-based drugs (SGL2, GLP1) * Severe valvular heart disease * BMI \> 50kg/m2 * Other debilitating illness that would preclude participation * Any contra-indication to MRI * Any contra-indication to muscle biopsies. Group 2 * Age \< 18 years * BMI \> 50 kg/m2 * Atrial fibrillation with poorly controlled heart rate * PDE5 inhibitor use * Severe valvular disease * Severe COPD * CKD 4 or higher * Currently taking incretin-based drugs (SGL2, GLP1) * Any contra-indication to MRI * Any contra-indication to muscle biopsies.

Treatments and study arms

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.

Primary outcomes

Peak muscle perfusion during exercisePre intervention (Day 1)

Peak muscle perfusion (Aβ) during exercise will be assessed by Contrast enhanced ultrasound (CEU)

Peak muscle perfusion during exercisePost intervention (Post Day 1)

Peak muscle perfusion (Aβ) during exercise will be assessed by Contrast enhanced ultrasound (CEU)

Single cell RNA sequencing of skeletal musclePre intervention (Day 2)

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

Single cell RNA sequencing of skeletal musclePost intervention (Day 2)

Muscle to fat ratio of legPre intervention (Day 3)

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)

Peak change in microvascular perfusion from rest to exercisePre intervention (Day 3)

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

Muscle to fat ratio of legPost intervention (Day 3)

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

Peak change in microvascular perfusion from rest to exercisePost intervention (Day 3)

Study locations

1 locations were listed when this page was built. The first 40 are shown.

University of Texas Southwestern Medical Center🇺🇸 Dallas, Texas, United States

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