Exercise Intolerance in Elderly Patients With HFpEF(Heart Failure With Preserved Ejection Fraction)

Study Overview
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Brief Summary
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The purpose of this study is to examine the effects of weight loss via hypocaloric diet (CR)and aerobic exercise (AT) compared to the effects of weight loss via hypocaloric diet (CR), aerobic training (AT)and resistance training (RT).

Detailed Description
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Heart failure with preserved ejection fraction (HFPEF) is the most common form of HF, is nearly unique to the older population, particularly older women, and is increasing in prevalence. Exercise intolerance, with severe exertional dyspnea and fatigue, is the primary manifestation of chronic HFPEF and is a major determinant of these patients' severely reduced quality of life (QOL). However, its pathophysiology is poorly understood and its optimal treatment remains undefined. Our recent data and others' indicate that in older HFPEF patients, both increased adiposity and abnormalities in skeletal muscle are major contributors to exercise intolerance and potential therapeutic targets. Obesity is one of the strongest risk factors for HFPEF, and is a robust predictor of physical disability in older persons. The investigator recently reported that in HFPEF compared to age-matched controls, percent total and leg lean mass are significantly reduced and independently predict exercise capacity. Using MRI and needle biopsy of the thigh muscle, the investigators found increased fat infiltration, reduced capillary density and percent type I oxidative fibers, and trends for reduced muscle mitochondrial mass and function. Reduced exercise capacity was related to each of these muscle abnormalities, supporting their important role in HFPEF. Diet, with or without aerobic exercise, can increase exercise capacity and quality of life in older obese persons with a variety of disorders, but usually results in significant loss of skeletal muscle mass, which could potentially have adverse long term consequences. The purpose of this trial is to determine if addition of resistance training to diet plus aerobic exercise training can improve skeletal muscle mass and function in HFPEF. Multiple lines of evidence and our preliminary data indicate that resistance training (RT) may be an ideal addition to CR+AT for HFPEF, since RT reliably increases muscle mass, quality, strength, and function, significantly more than AT, and can prevent nearly 50% of the muscle mass loss during CR. Therefore, the primary aim of the proposed study is to conduct a randomized, single-blinded 20-week intervention trial of RT added to CR+AT in 84 overweight / obese (BMI greater than 28 kg/m2), older (age greater than 60 years) HFPEF patients to test the following primary hypothesis: The addition of resistance training to CR+AT will improve exercise capacity.

Official Title
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Study of the Effects Caloric Restriction and Exercise Training in Patients With Heart Failure and a Normal Ejection Fraction

Conditions
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Obesity, Heart Failure, Diastolic

Intervention / Treatment
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* Behavioral: dietary, aerobic and resistance training
* Behavioral: dietary, and aerobic exercise


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 60 years or older Ejection fraction ≥ 50% Left Ventricular Diastolic Dysfunction ≥ grade 1 BMI ≥ 28 kg/m2 HF symptoms/ signs by cardiologist review, using NHANES HF Clinical Score >/= 3 or Rich et al. criteria for HF Exclusion Criteria: Valvular heart disease as the primary etiology of CHF (congestive heart failure) Significant change in cardiac medication or Heart Failure symptoms <6 weeks Hospitalization or urgent care visit <6 weeks Uncontrolled hypertension Uncontrolled diabetes Evidence of significant Chronic Obstructive Pulmonary Disease (COPD) Recent or debilitating stroke Cancer or other noncardiovascular conditions with life expectancy less than 2 years Significant anemia (<10 g/dL Hgb) Significant renal insufficiency (eGFR <30 mL/min/1.73m2) Pregnant or of child-bearing potential Psychiatric disease- uncontrolled major psychoses, depressions, dementia, or personality disorder Plans to leave area within the study period Refuses informed consent -

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: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: dietary, and aerobic exercise<br>Intervention for diet-A hypocaloric diet will be developed to achieve a 2800 kcal/week deficit, which should produce about 0.4 kg (1 lb.) weight loss per week. Intervention for aerobic exercise-Based on initial evaluations and the stress testing results, (HR, VO2, RPE) an individual exercise prescription will be developed for aerobic training. | Behavioral: dietary, and aerobic exercise<br>* hypocaloric diet individual prescription for aerobic training.<br>|
| Active Comparator: dietary, aerobic and resistance training<br>Intervention for diet-A hypocaloric diet will be developed to achieve a 2800 kcal/week deficit, which should produce about 0.4 kg (1 lb.) weight loss per week. Intervention for aerobic exercise-Based on initial evaluations and the stress testing results, (HR, VO2, RPE) an individual exercise prescription will be developed for aerobic training. Intervention for resistance training- Additional weight resistant exercise will be added to this arm. | Behavioral: dietary, aerobic and resistance training<br>* hypocaloric diet individual exercise prescription for aerobic training individual exercise prescription for resistance training.<br>Behavioral: dietary, and aerobic exercise<br>* hypocaloric diet individual prescription for aerobic training.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Peak Exercise Oxygen Consumption (VO2) | Peak exercise oxygen consumption (VO2) pre and post intervention | 20 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Skeletal Muscle Mass | Measure skeletal muscle mass in kg by DEXA analysis pre and post intervention. | 20 weeks | 
| Thigh Skeletal Muscle Mass | Measure skeletal muscle mass by MRI analysis pre and post intervention. | 20 weeks | 
| Thigh Muscle Composition | MRI skeletal muscle to intermuscular fat ratio | 20 weeks | 
| Muscle Strength | maximal isokinetic knee extensor strength (Newton-meters, Nm) using an isokinetic dynamometer (Biodex®) | 20 weeks | 
| Muscle Quality | knee extensor strength to thigh muscle area assessed by MRI (Nm/cm2). | 20 weeks | 
| Quality of Life Measured by Kansas City Cardiomyopathy Questionnaire (KCCQ) Overall Summary Score | The KCCQ Overall Summary Summary Score is a heart failure disease-specific quality of life measure encompassing domains of physical limitation, HF symptoms, quality of life, and social limitation scored on a scale of 0-100 with higher scores indicating better health status. | 20 weeks | 
| Quality of Life Measured by Short Form 36 Item Questionnaire (SF-36) | The SF-36 is a quality of life assessment with 2 component scores (Physical Composite Score and Mental Composite Score) ranging 0-100 with higher scores indicating better health status. | 20 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Diastolic heart failure, Heart Failure, Elderly, Obesity