Heart Failure, Diastolic, Obesity
Conditions
Keywords
Diastolic heart failure, Heart Failure, Elderly, Obesity
Brief summary
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
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.
Interventions
hypocaloric diet individual exercise prescription for aerobic training individual exercise prescription for resistance training.
hypocaloric diet individual prescription for aerobic training.
Sponsors
Study design
Eligibility
Inclusion criteria
1. Age 60 years or older 2. Ejection fraction ≥ 50% 3. Left Ventricular Diastolic Dysfunction ≥ grade 1 4. BMI ≥ 28 kg/m2 5. HF symptoms/ signs by cardiologist review, using NHANES HF Clinical Score \>/= 3 or Rich et al. criteria for HF
Exclusion criteria
1. Valvular heart disease as the primary etiology of CHF (congestive heart failure) 2. Significant change in cardiac medication or Heart Failure symptoms \<6 weeks 3. Hospitalization or urgent care visit \<6 weeks 4. Uncontrolled hypertension 5. Uncontrolled diabetes 6. Evidence of significant Chronic Obstructive Pulmonary Disease (COPD) 7. Recent or debilitating stroke 8. Cancer or other noncardiovascular conditions with life expectancy less than 2 years 9. Significant anemia (\<10 g/dL Hgb) 10. Significant renal insufficiency (eGFR \<30 mL/min/1.73m2) 11. Pregnant or of child-bearing potential 12. Psychiatric disease- uncontrolled major psychoses, depressions, dementia, or personality disorder 13. Plans to leave area within the study period 14. Refuses informed consent -
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Peak Exercise Oxygen Consumption (VO2) | 20 weeks | Peak exercise oxygen consumption (VO2) pre and post intervention |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Muscle Quality | 20 weeks | knee extensor strength to thigh muscle area assessed by MRI (Nm/cm2). |
| Skeletal Muscle Mass | 20 weeks | Measure skeletal muscle mass in kg by DEXA analysis pre and post intervention. |
| Thigh Skeletal Muscle Mass | 20 weeks | Measure skeletal muscle mass by MRI analysis pre and post intervention. |
| Thigh Muscle Composition | 20 weeks | MRI skeletal muscle to intermuscular fat ratio |
| Quality of Life Measured by Kansas City Cardiomyopathy Questionnaire (KCCQ) Overall Summary Score | 20 weeks | 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. |
| Quality of Life Measured by Short Form 36 Item Questionnaire (SF-36) | 20 weeks | 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. |
| Muscle Strength | 20 weeks | maximal isokinetic knee extensor strength (Newton-meters, Nm) using an isokinetic dynamometer (Biodex®) |
Other
| Measure | Time frame | Description |
|---|---|---|
| Mitochondrial Content | 20 weeks | Porin citrate synthase pre and post intervention. |
| Mitochondrial Function | 20 weeks | respiratory control ratio and mitofusin 2 concentration.pre and post intervention. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Dietary, and Aerobic Exercise 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.
dietary, and aerobic exercise: hypocaloric diet individual prescription for aerobic training. | 44 |
| Dietary, Aerobic and Resistance Training 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.
dietary, aerobic and resistance training: hypocaloric diet individual exercise prescription for aerobic training individual exercise prescription for resistance training.
dietary, and aerobic exercise: hypocaloric diet individual prescription for aerobic training. | 44 |
| Total | 88 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 2 | 2 |
| Overall Study | Lost to Follow-up | 1 | 0 |
| Overall Study | Non-compliance | 1 | 1 |
| Overall Study | Personal reasons | 2 | 0 |
Baseline characteristics
| Characteristic | Dietary, Aerobic and Resistance Training | Dietary, and Aerobic Exercise | Total |
|---|---|---|---|
| Age, Continuous | 69.7 years STANDARD_DEVIATION 5.8 | 67.9 years STANDARD_DEVIATION 5.4 | 68.8 years STANDARD_DEVIATION 5.7 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 44 Participants | 44 Participants | 88 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Peak exercise oxygen consumption (VO2) | 1530 ml/min STANDARD_DEVIATION 366 | 1529 ml/min STANDARD_DEVIATION 375 | 1530 ml/min STANDARD_DEVIATION 368 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 23 Participants | 24 Participants | 47 Participants |
| Race (NIH/OMB) More than one race | 1 Participants | 1 Participants | 2 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 20 Participants | 19 Participants | 39 Participants |
| Region of Enrollment United States | 44 Participants | 44 Participants | 88 Participants |
| Sex: Female, Male Female | 38 Participants | 37 Participants | 75 Participants |
| Sex: Female, Male Male | 6 Participants | 7 Participants | 13 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 44 | 0 / 44 |
| other Total, other adverse events | 24 / 44 | 25 / 44 |
| serious Total, serious adverse events | 6 / 44 | 6 / 44 |
Outcome results
Peak Exercise Oxygen Consumption (VO2)
Peak exercise oxygen consumption (VO2) pre and post intervention
Time frame: 20 weeks
Population: Analysis completed on all participants with peak VO2 obtained (n=77).
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Dietary, and Aerobic Exercise | Peak Exercise Oxygen Consumption (VO2) | 1609 ml/min | Standard Error 24 |
| Dietary, Aerobic, and Resistance Training | Peak Exercise Oxygen Consumption (VO2) | 1653 ml/min | Standard Error 24 |
Muscle Quality
knee extensor strength to thigh muscle area assessed by MRI (Nm/cm2).
Time frame: 20 weeks
Population: Analysis completed on all participants with MRI and Biodex measurements.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Dietary, and Aerobic Exercise | Muscle Quality | 0.90 Nm/cm^2 | Standard Error 0.02 |
| Dietary, Aerobic, and Resistance Training | Muscle Quality | 0.97 Nm/cm^2 | Standard Error 0.02 |
Muscle Strength
maximal isokinetic knee extensor strength (Newton-meters, Nm) using an isokinetic dynamometer (Biodex®)
Time frame: 20 weeks
Population: Analysis completed on all participants with Biodex measures.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Dietary, and Aerobic Exercise | Muscle Strength | 97.5 Nm | Standard Error 2.3 |
| Dietary, Aerobic, and Resistance Training | Muscle Strength | 103.9 Nm | Standard Error 2.2 |
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.
Time frame: 20 weeks
Population: Analysis completed on all participants with KCCQ assessment.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Dietary, and Aerobic Exercise | Quality of Life Measured by Kansas City Cardiomyopathy Questionnaire (KCCQ) Overall Summary Score | 91 score on a scale | Standard Error 2 |
| Dietary, Aerobic, and Resistance Training | Quality of Life Measured by Kansas City Cardiomyopathy Questionnaire (KCCQ) Overall Summary Score | 87 score on a scale | Standard Error 2 |
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.
Time frame: 20 weeks
Population: Analysis completed on all participants with SF-36 assessment.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Dietary, and Aerobic Exercise | Quality of Life Measured by Short Form 36 Item Questionnaire (SF-36) | 47.4 score on a scale | Standard Error 1.4 |
| Dietary, Aerobic, and Resistance Training | Quality of Life Measured by Short Form 36 Item Questionnaire (SF-36) | 46.9 score on a scale | Standard Error 1.3 |
Skeletal Muscle Mass
Measure skeletal muscle mass in kg by DEXA analysis pre and post intervention.
Time frame: 20 weeks
Population: Analysis completed on all participants with DEXA measurement (n=78).
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Dietary, and Aerobic Exercise | Skeletal Muscle Mass | 49.4 kg | Standard Error 0.3 |
| Dietary, Aerobic, and Resistance Training | Skeletal Muscle Mass | 49.4 kg | Standard Error 0.3 |
Thigh Muscle Composition
MRI skeletal muscle to intermuscular fat ratio
Time frame: 20 weeks
Population: Analysis completed on all participants with MRI measurements.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Dietary, and Aerobic Exercise | Thigh Muscle Composition | 4.0 ratio | Standard Error 0.1 |
| Dietary, Aerobic, and Resistance Training | Thigh Muscle Composition | 4.0 ratio | Standard Error 0.1 |
Thigh Skeletal Muscle Mass
Measure skeletal muscle mass by MRI analysis pre and post intervention.
Time frame: 20 weeks
Population: Analysis completed on all participants with thigh MRI.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Dietary, and Aerobic Exercise | Thigh Skeletal Muscle Mass | 108.5 cm^2 | Standard Error 1.2 |
| Dietary, Aerobic, and Resistance Training | Thigh Skeletal Muscle Mass | 108.9 cm^2 | Standard Error 1.1 |
Mitochondrial Content
Porin citrate synthase pre and post intervention.
Time frame: 20 weeks
Mitochondrial Function
respiratory control ratio and mitofusin 2 concentration.pre and post intervention.
Time frame: 20 weeks