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.
Age range
18 Years
Sex
ALL
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A starting point for the conversation — always confirm anything about your own eligibility, costs, and care with the study team and your doctor.
Peak muscle perfusion during exercise
Timeframe: Pre intervention (Day 1)
Peak muscle perfusion during exercise
Timeframe: Post intervention (Post Day 1)
Single cell RNA sequencing of skeletal muscle
Timeframe: Pre intervention (Day 2)
Single cell RNA sequencing of skeletal muscle
Timeframe: Post intervention (Day 2)
Muscle to fat ratio of leg
Timeframe: Pre intervention (Day 3)
Peak change in microvascular perfusion from rest to exercise
Timeframe: Pre intervention (Day 3)
Muscle to fat ratio of leg
Timeframe: Post intervention (Day 3)
Peak change in microvascular perfusion from rest to exercise
Timeframe: Post intervention (Day 3)