Exercise Training for Heart Failure
Trial Summary
What is the purpose of this trial?
Heart failure with preserved ejection fraction (HFpEF) accounts for approximately half of the heart failure population in the United States. The primary chronic symptom in patients with HFpEF is severe exercise intolerance quantified as reduced peak oxygen uptake during whole body exercise (peak V̇O2). To date, studies have focused almost exclusively on central cardiac limitations of peak V̇O2 in HFpEF. However, in stark contrast to heart failure with reduced ejection fraction (HFrEF), drug therapies targeting central limitations have invariably failed to improve peak V̇O2, quality of life, or survival in HFpEF. Emerging evidence from our lab suggests reduced skeletal muscle oxidative capacity may contribute to exercise intolerance in HFpEF patients. However, the mechanisms responsible for peripheral metabolic inefficiency remain unclear. Reduced blood flow (oxygen delivery), and slowed oxygen uptake kinetics (O2 utilization) may both contribute to reduced peripheral oxidative capacity. Importantly, reduced oxidative capacity may result in increased production of metabolites known to activate muscle afferent nerves and stimulate reflex increases in muscle sympathetic (vasoconstrictor) nervous system activity (MSNA). However, to date there have been no studies specifically investigating the contribution of peripheral metabolic and neural impairments to reduced exercise capacity in HFpEF. The overall aim of this proposal will be 1) to identify impairments in peripheral vascular, metabolic, and sympathetic neural function and 2) to assess the ability of small muscle mass (knee extensor, KE) training, specifically targeting these peripheral skeletal muscle deficiencies, to improve aerobic capacity and exercise tolerance in HFpEF. GLOBAL HYPOTHESIS 1: HFpEF patients will demonstrate reduced skeletal muscle oxygen delivery, slowed oxygen uptake kinetics, and elevated resting and metaboreflex mediated MSNA. Hypothesis 1.1: The vasodilatory response to knee extensor exercise will be impaired in HFpEF patients. Specific Aim 1.1: To measure the immediate rapid onset vasodilatory response to muscle contraction, as well as the dynamic onset, and steady state vasodilatory responses to dynamic KE exercise. Hypothesis 1.2: Skeletal muscle oxygen uptake kinetics will be slowed in HFpEF. Specific Aim 1.2: To measure pulmonary oxygen uptake kinetics during isolated KE exercise in order to isolate peripheral impairments in metabolic function independent of any central impairment. Hypothesis 1.3: HFpEF patients will demonstrate elevated MSNA at rest, and exaggerated metaboreflex sensitivity during exercise. Specific Aim 1.3: To test this hypothesis the investigators will measure MSNA from the peroneal nerve at rest, and during post exercise ischemia to directly assess metaboreflex sensitivity in HFpEF. GLOBAL HYPOTHESIS 2: Isolating peripheral adaptations to exercise training using single KE exercise training will improve peripheral vascular, metabolic, and neural function and result in greater functional capacity in HFpEF. Hypothesis 2.1: Isolated KE exercise training will improve the vasodilatory response to exercise, speed oxygen uptake kinetics, and reduce MSNA at rest HFpEF. Specific Aim 2.1: The assessments of vascular, metabolic, and neural function proposed in hypothesis 1 will be repeated after completing 8 weeks of single KE exercise training. Hypothesis 2.2: Single KE exercise training will improve whole body exercise tolerance, peak V̇O2, and functional capacity in HFpEF. Specific Aim 2.2: To test this hypothesis the investigators will measure maximal single KE work rate, V̇O2 kinetics and peak V̇O2 during cycle exercise, as well as distance covered in the six minute walk test.
Eligibility Criteria
This trial is for people over 65 with heart failure where the heart pumps normally but fills abnormally (HFpEF). They must show signs of heart failure, have a normal ejection fraction (>0.50), and evidence of diastolic dysfunction. Excluded are those with severe lung or advanced heart diseases, certain arrhythmias, heavy exercise habits, recent smokers, kidney issues, or on specific heart medications.Inclusion Criteria
Exclusion Criteria
Timeline
Screening
Participants are screened for eligibility to participate in the trial
Baseline Assessment
Initial assessments of vascular, metabolic, and neural function
Treatment
Participants undergo 8 weeks of single knee extensor exercise training
Post-Treatment Assessment
Re-assessment of vascular, metabolic, and neural function after exercise training
Follow-up
Participants are monitored for changes in exercise tolerance and physiological responses
Treatment Details
Interventions
- Exercise training
Find a Clinic Near You
Who Is Running the Clinical Trial?
University of Texas Southwestern Medical Center
Lead Sponsor