Muscle, Essential Amino Acids, and eXercise in Heart Failure

Study Overview
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Brief Summary
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Half of heart failure patients have preserved ejection fraction (HFpEF). Like patients with reduced ejection fraction (HFrEF), HFpEF patients suffer from exercise intolerance (low VO2max), which reduces physical function, quality of life, and survival. Strikingly, there is no medication proven to increase survival for HFpEF patients. Whereas exercise intolerance in HFrEF patients is the result of cardiovascular limitations, physical dysfunction in HFpEF patients is largely the result of peripheral abnormalities in skeletal muscle. Indeed, research in HFpEF patients identified that physical function and VO2peak are directly related to leg lean mass, and drugs focused on improving cardiovascular function have failed to improve VO2peak. Unfortunately, no therapy has been identified for this population that can concurrently improve cardiovascular and muscle health. The need for improved muscle therapies is reinforced by the fact that HFpEF patients are commonly older adults who are predisposed to muscle wasting. Strategic essential amino acid (EAA) ingestion has been shown to improve the adaptive response of muscle to exercise. Therefore, the investigators will determine, in HFpEF patients, the extent to which ingesting a strategic mixture of EAAs during an acute aerobic exercise training program enhances the response to this exercise strategy.

Official Title
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Cost-effective Strategies to Improve Rehabilitative Outcomes for Heart Failure Patients With Preserved Ejection Fraction

Conditions
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Heart Failure, Diastolic

Intervention / Treatment
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* Other: Exercise
* Dietary Supplement: Essential Amino Acids
* Dietary Supplement: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 60+ years of age Able to communicate meaningfully with the investigator and must be legally competent to provide written informed consent. Diagnosed with HFpEF as per established echocardiographic criteria (New York Heart Association Class II-III). Exclusion Criteria: Unstable angina, myocardial infarction in the past 4 weeks Uncompensated heart failure New York Heart Association class IV symptoms, complex ventricular arrhythmias, symptomatic severe aortic stenosis, acute pulmonary embolus, acute myocarditis, untreated high-risk proliferative retinopathy, recent retinal hemorrhage, uncontrolled hypertension, baseline blood screening abnormalities Medication non-compliance Medical / orthopedic conditions precluding exercise Exercise training (>2 weekly sessions of moderate to high intensity aerobic or resistance exercise) Subjects on anti-coagulation medication will not be eligible for the muscle biopsy procedure, but are deemed eligible for study participation if INR < 3.

Ages Eligible for Study
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Minimum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Essential Amino Acid and Exercise<br>Participants will be provided with essential amino acids during exercise training. | Other: Exercise<br>* Aerobic exercise performed 3/d per week during intervention<br>Dietary Supplement: Essential Amino Acids<br>* Mixture of 10g of essential amino acids ingested throughout intervention<br>|
| Placebo Comparator: Placebo and Exercise<br>Participants will be provided with placebo supplement during exercise training. | Other: Exercise<br>* Aerobic exercise performed 3/d per week during intervention<br>Dietary Supplement: Placebo<br>* 10g of maltodextrin ingested throughout intervention<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in VO2max | Change in maximal Aerobic Capacity | Change from pre to after the 4 week intervention | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Flow-mediated Dilation | Change in blood vessel function | Change from pre to after the 4 week intervention | 
| Change in Pulse wave velocity | Change in pulse wave velocity | Change from pre to after the 4 week intervention | 
| Change in Diastolic Function | Change in diastolic Function | Change from pre to after the 4 week intervention | 
| Change in Skeletal Muscle mRNA expression | Change in skeletal Muscle mRNA expression | Change from pre to after the 4 week intervention |