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Mechanisms of Exercise Intolerance in Heart Failure With Preserved Ejection Fraction

Not Applicable
Active, not recruiting
Conditions
Heart Failure, Diastolic
Interventions
Behavioral: Exercise training
Registration Number
NCT04068844
Lead Sponsor
University of Texas Southwestern Medical Center
Brief Summary

The global objective of this study is to determine the mechanisms of exercise intolerance and dyspnea on exertion (DOE) in patients with HFpEF and based on this pathophysiology, test whether specific exercise training programs (whole body vs single leg) will result in improved exercise tolerance.

Detailed Description

This will be a randomized, non-blinded prospective intervention testing the effects of two types of exercise training, whole body and isolated single leg, on HFpEF patients with either central or peripheral limitations to exercise training. Subjects will undergo baseline maximal exercise testing and invasive right heart catheterization to define exercise tolerance and pulmonary and cardiac pressures during exercise. Based on the results of baseline testing, subjects will be divided into either centrally limited, defined as excessive rise in pulmonary capillary wedge pressure more than 25 mmHg that decreases after administration of sub-lingual nitroglycerin resulting in improved exercise tolerance, or peripherally limited, defined as no improvement in exercise tolerance despite reduction in pulmonary capillary wedge pressure after sublingual nitroglycerin. After baseline testing, subjects will be randomized to either whole body cycle exercise supplemented with sublingual nitroglycerin to improve training responsiveness or isolated single leg exercise training for 4 months. After 4 months, subjects will repeat maximal exercise testing and invasive right heart catheterization to assess responses to 4 months of exercise training.

Recruitment & Eligibility

Status
ACTIVE_NOT_RECRUITING
Sex
All
Target Recruitment
93
Inclusion Criteria
  • signs and symptoms of heart failure
  • an ejection fraction > 0.50
  • objective evidence of diastolic dysfunction
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Exclusion Criteria
  • age < 60 years
  • BMI > 50 kg/m2
  • PDE5 inhibitor use
  • Severe valvular disease
  • Severe COPD
  • CKD 4 or higher
  • Contra-indication to MRI.
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Study & Design

Study Type
INTERVENTIONAL
Study Design
FACTORIAL
Arm && Interventions
GroupInterventionDescription
Peripheral HFpEF whole body exerciseExercise trainingHFpEF patients who have a peripheral limitation as the cause of the exercise intolerance randomized to whole body cycle training.
Central HFpEF whole body exerciseExercise trainingHFpEF patients who have a central limitation as the cause of the exercise intolerance randomized to whole body cycle training.
Central HFpEF isolated single leg exerciseExercise trainingHFpEF patients who have a central limitation as the cause of the exercise intolerance randomized to isolated single leg training.
Peripheral HFpEF isolated single leg exerciseExercise trainingHFpEF patients who have a peripheral limitation as the cause of the exercise intolerance randomized to isolated single leg training.
Primary Outcome Measures
NameTimeMethod
Aerobic fitness4 months

Change in peak VO2 after exercise training

Secondary Outcome Measures
NameTimeMethod
Sympathetic activity4 months

Change in muscle sympathetic activity

Cardiac fibrosis4 months

Change in T1 mapping times by cardiac MRI

Cardiopulmonary hemodynamics4 months

Change in exercise pulmonary capillary wedge pressure

Leg blood flow4 months

Change in leg blood flow assessed by Doppler velocities in femoral artery

Trial Locations

Locations (1)

The Institute for Exercise and Environmental Medicine

🇺🇸

Dallas, Texas, United States

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