Mechanisms of Exercise Intolerance in Heart Failure With Preserved Ejection Fraction

Not Applicable

Active, not recruiting

• Conditions: Heart Failure, Diastolic

• 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.

Study Timeline

• Study Start: 2019-08-01
• Study First Submitted: 2019-08-22
• Study First Submitted QC: 2019-08-23
• Study First Posted: 2019-08-28
• Status Verified: 2024-12
• Last Update Submitted: 2024-12-30
• Last Update Posted: 2025-01-01
• Primary Completion: 2025-08-01
• Study Completion: 2025-12-31

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

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: FACTORIAL

Primary Outcome Measures

Name	Time	Method
Aerobic fitness	4 months	Change in peak VO2 after exercise training

Secondary Outcome Measures

Name	Time	Method
Sympathetic activity	4 months	Change in muscle sympathetic activity
Cardiac fibrosis	4 months	Change in T1 mapping times by cardiac MRI
Cardiopulmonary hemodynamics	4 months	Change in exercise pulmonary capillary wedge pressure
Leg blood flow	4 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