The Effect of Adiposity on Muscle and Microvascular Function in HFpEF

Trial details

Who runs it

University of Texas Southwestern Medical Center

Trial code

NCT06930495

Record updated

3 September 2026

Original description

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.Read full original descriptionShow less

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.

Inclusion: 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: Currently taking incretin-based drugs (SGL2, GLP1); PDE5 inhibitor use; Currently taking incretin-based drugs (SGL2, GLP1); NYHA Class IV chronic heart failure; Unstable coronary artery disease; Uncontrolled arrhythmia; Severe valvular heart disease; Other debilitating illness that would preclude participation; Atrial fibrillation with poorly controlled heart rate; Severe valvular disease; Prior history of reduced ejection fraction (<50%); Age < 18 years; Group 1; Infiltrative cardiomyopathy; Left bundle branch block; CKD 4 or higher; BMI > 50kg/m2; Any contra-indication to MRI; Any contra-indication to muscle biopsies; Group 2; BMI > 50 kg/m2; Severe COPD; CKD 4 or higher; Any contra-indication to MRI; Any contra-indication to muscle biopsies.

ClinicalTrials.gov NCT06930495