The Effect of Adiposity on Muscle and Microvascular Function in HFpEF

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. 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.

Conditions

Heart Failure With Preserved Ejection Fraction (HFPEF)

Study Overview

Study Details

Study overview

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.

The Effect of Adiposity on Muscle and Microvascular Function in HFpEF

The Effect of Adiposity on Muscle and Microvascular Function in HFpEF

Condition
Heart Failure With Preserved Ejection Fraction (HFPEF)
Intervention / Treatment

-

Contacts and Locations

Dallas

University of Texas Southwestern Medical Center, Dallas, Texas, United States, 75390

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

For general information about clinical research, read Learn About Studies.

Eligibility Criteria

  • * 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
  • * Adults who do not have heart failure with preserved ejection fraction
  • * Age ≥ 18 years
  • * 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.
  • * 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.

Ages Eligible for Study

18 Years to

Sexes Eligible for Study

ALL

Accepts Healthy Volunteers

Yes

Collaborators and Investigators

University of Texas Southwestern Medical Center,

Christopher M Hearon Jr, PhD, PRINCIPAL_INVESTIGATOR, University of Texas Southwestern Medical Center

Study Record Dates

2026-06-01