Clinical trial NCT04068844: Mechanisms of Exercise Intolerance in Heart Failure With Preserved Ejection Fraction
Official title: Mechanisms of Exercise Intolerance in Heart Failure With Preserved Ejection Fraction
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: NA
Conditions: Heart Failure, Diastolic
Keywords: Exercise
Hemodynamics,
Heart failure
Lead sponsor: University of Texas Southwestern Medical Center
Sponsor class: OTHER
Collaborators: name: The University of Texas at Arlington
First posted: 2019-08-28
Enrollment: 93
Sex: ALL
Minimum age (years): 60
Maximum age (years): 90
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: FACTORIAL
Intervention model description: HFpEF patients with either central or peripheral limitations to exercise will be randomly assigned to either whole body or isolated single leg exercise.
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Aerobic fitness
timeFrame: 4 months
Secondary outcomes:
measure: Cardiopulmonary hemodynamics
timeFrame: 4 months
measure: Sympathetic activity
timeFrame: 4 months
measure: Leg blood flow
timeFrame: 4 months
measure: Cardiac fibrosis
timeFrame: 4 months
Other outcomes:
Locations:
city: Dallas
country: United States
facility: The Institute for Exercise and Environmental Medicine
state: Texas
Study officials:
References: