Mechanisms of Exercise Intolerance in Heart Failure With Preserved Ejection Fraction

The University of Texas System (UT)

Status: Active, not recruiting

Conditions: Heart Failure, Diastolic

Treatments: Behavioral: Exercise training

Study type: Interventional

Funder types: Other

Identifiers

NCT04068844

STU-2019-0617

Details and patient eligibility

About

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.

Full 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.

Enrollment: 93 patients

Sex: All

Ages: 60 to 90 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Factorial Assignment

Masking: None (Open label)

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93 participants in 4 patient groups

Central HFpEF whole body exercise

Experimental group

Description:

HFpEF patients who have a central limitation as the cause of the exercise intolerance randomized to whole body cycle training.

Treatment:

Behavioral: Exercise training

Central HFpEF isolated single leg exercise

Experimental group

Description:

HFpEF patients who have a central limitation as the cause of the exercise intolerance randomized to isolated single leg training.

Treatment:

Behavioral: Exercise training

Peripheral HFpEF whole body exercise

Experimental group

Description:

HFpEF patients who have a peripheral limitation as the cause of the exercise intolerance randomized to whole body cycle training.

Treatment:

Behavioral: Exercise training

Peripheral HFpEF isolated single leg exercise

Experimental group

Description:

HFpEF patients who have a peripheral limitation as the cause of the exercise intolerance randomized to isolated single leg training.

Treatment:

Behavioral: Exercise training