Heart Failure
Conditions
Keywords
Heart failure, Exercise, Cardiopulmonary
Brief summary
The purpose of this research study is to better understand how exercise training in older adults (≥65 years) with heart failure (HF) affects skeletal muscle both intrinsically and in respect to its impact on functional capacity. While many conceptualize HF as a pathophysiology that exclusively affects the heart, skeletal muscle atrophy and weakening are also elemental to the disease. While reduced exercise capacity is typically associated with HF, this may be related more to disease effects in skeletal muscle than the heart. This is a clinical study that focuses on exercise training which compares functional endpoints before and after training. Patients are randomized to one of three exercise training interventions (aerobic vs. aerobic and strength vs. inspiratory muscle training) for 12 weeks and are assessed pre- and post-training to determine if any differences occur in their skeletal muscle and functional capacity. Skeletal muscle biopsies before and after the exercise training intervention in order to study changes in skeletal muscle histology and biology. Functional endpoints in this study include ventilatory gas indices from cardiopulmonary exercise testing, lower body strength testing, grip strength, sit-to-stand, six-minute-walk distance, gait speed, inspiratory muscle strength, and quality of life and physical activity-oriented questionnaires, including the Kansas City Cardiomyopathy Questionnaire, Duke Activity Status Index, and CHAMPS Physical Activity Questionnaire for Older Adults. Body composition is measured with Dual Energy X-ray (DXA) scanning. Skeletal muscle biopsies are completed in the vastus lateralis of the non-dominant leg to assess histology and biologic endpoints.
Detailed description
Despite decades of research, HF remains a common disease that continues to rise in prevalence, particularly among the expanding population of older adults. By virtue of age, older adults are prone to higher incidence of HF and worse clinical consequences. Exercise intolerance and dyspnea are common symptoms that portend poor prognosis, and which erode functional independence and quality of life. Mortality and morbidity also increase significantly as functional capacity declines. Growing evidence suggests that pathophysiology of central cardiac dysfunction is linked to skeletal muscle pathophysiology. While HF therapeutic guidelines primarily emphasize steps that improve cardiac parameters, and/or volume status, goals to modify HF skeletal muscle myopathy may constitute a vital complementary treatment target. Ongoing analyses from our pilot VA Merit investigation provide pertinent insights and substantiation. The investigators demonstrated reduced functional capacity (both aerobic and strength) in 31 HF patients (mean age 66 years) compared to 39 age-matched healthy controls (mean age 67). The investigators also showed increased expression of genes signaling ubiquitin-mediated proteolysis in skeletal muscle in relation to decreasing aerobic and strength performance. Consistently, reduced lean muscle mass, as measured by DXA, correlated to the reduced strength indices. This proposal constitutes a logical progression of this pilot analysis and follows the analytic path the investigators anticipated. Whereas the initial work characterized key skeletal muscle gene expression patterns in association to disease, exercise capacity, and body composition, this study compares the effects of three exercise training regimens (i.e., aerobic vs. combined aerobic and strength vs. inspiratory muscle training \[IMT\]) each with a unique physiological rationale. The investigators will explore differences in how each training regimen modifies clinical attributes (function/symptoms) as well as skeletal muscle biology that likely underlie these differences. These insights will help identify therapeutic strategies that better suppress injurious disease mechanisms and thereby facilitate improved clinical outcomes and quality of life. Specific Aims: a. To assess differences in functional outcomes (peak oxygen utilization \[VO2\]) and one-repetition max \[1RM\]) relative to different training regimens: a. Aerobic vs. Aerobic-Strength vs. inspiratory Muscle Training (IMT). i. Analyses will include assessments of training differences in respect to broader functional parameters (aerobic, strength, inspiration), symptoms, and quality of life. b. To assess gene expression in relation to the different training regimens.
Interventions
BEHAVIORALAerobic Exercise Intervention
Aerobic Exercise Intervention - 12 weeks of a minimum of 3 days a week for 60 minutes of aerobic exercise
BEHAVIORALCombined Aerobic and Strength Exercise Intervention
Combined Aerobic and Strength Exercise Intervention- 12 weeks of a minimum of 3 days a week for 60 minutes of Combined Aerobic and Strength Exercise
BEHAVIORALInspiratory Muscle Training Exercise Intervention
Inspiratory Muscle Training Exercise Intervention- 12 weeks of a minimum of 3 days a week for 60 minutes of Inspiratory Muscle Training Exercise
Sponsors
VA Office of Research and Development
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Participants with heart failure will complete 1 of 3 exercise training interventions (aerobic vs. aerobic and strength vs. inspiratory) for 12 weeks and will be assessed pre and post to determine if any differences occur in their skeletal muscle and functional capacity as part of the exercise intervention.
Eligibility
Sex/Gender
ALL
Age
50 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Diagnosis of Heart failure * Echo in two years * NYHA class II or III * Optimal therapy according to AHA/ACC and HFSA HF guidelines; unless documented by a provider for variation.
Exclusion criteria
* Major cardiovascular event or procedure within the prior 6 weeks. * Dementia * Severe COPD (FEV1\<50%), * End-stage malignancy * Severe valvular heart disease that would make exercise un safe * Orthopedic limitation preventing exercise * Any bleeding disorder that would contraindicate safe exercise * Women who are pregnant, breastfeeding, or likely to become pregnant within the next 6 months * Psychiatric hospitalization within the last 3 months * ICD device with heart rate limits that prohibit exercise assessments or exercise training. * Referring physicians will be provided with an opportunity to reprogram devices so that patients can participate. * Chronic use of oral corticosteroids or medications that affect muscle function. * Notably, patients using statins will be eligible, and this will be factored into the randomization and analysis. * Chronic ETOH or drug dependency shown within the last year
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| One Repetition Maximum- Leg Press | baseline and through study completion an average of 14 weeks | Leg press will be performed on the Keiser Leg press and measured in kilograms (kg) |
| Oxygen Uptake (VO2) Peak | baseline and through study completion an average of 14 weeks | a cardiopulmonary exercise test will be performed to determined peak VO2 in ML/KG/Min |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Skeletal Muscle Gene Expression | baseline and through study completion an average of 14 weeks | Skeletal muscle gene expression will be measured in RNA isolated from skeletal muscle biopsy samples via Illumina platform. The measure Number indicates the number of differentially expressed genes, and units are fold change over baseline. To investigate how the lifestyle interventions impacted gene expression at the mRNA level in skeletal muscles of our research participants we performed high-throughput RNA-Sequencing (Illumina HiSeq paired-end 150 base pairs). Differential gene expression analysis was performed on the RNA-seq. data using DeSEQ2 to determine differentially expressed genes (DEGs) between groups. All DEG analyses were performed using the Wald test (p \< 0.05) corrected for multiple comparisons using the Benjamini and Hochberg method. |
| Community Healthy Activities Model Program for Seniors (CHAMPS) Physical Activity Questionnaire for Older Adults - Frequency Component | baseline and through study completion an average of 12 weeks | Participants completed the Community Healthy Activities Model Program for Seniors (CHAMPS) Physical Activity Questionnaire for Older Adults as part of the Quality of Life and Daily Function study outcome. The CHAMPS questionnaire assesses duration and frequency of self-reported weekly physical activities of varying intensities in older adults. One component of the CHAMPS score is the frequency per week (i.e. number or count of events per week) that the participant reported that they engaged in all exercise related activities, and the frequency per week that the participant engaged in moderate-vigorous activities. The mean frequency of activities per week at baseline and follow-up for each study arm are reported here for the participants who completed both a baseline and follow-up assessment. A higher mean indicates a higher number of exercise-related activities were reported per week. |
| Community Healthy Activities Model Program for Seniors (CHAMPS) Physical Activity Questionnaire for Older Adults - Duration Component | baseline and through study completion an average of 12 weeks | Participants completed the Community Healthy Activities Model Program for Seniors (CHAMPS) Physical Activity Questionnaire for Older Adults as part of the Quality of Life and Daily Function study outcome. The CHAMPS questionnaire assesses duration and frequency of self-reported weekly physical activities of varying intensities in older adults. One component of the CHAMPS score is the self-reported duration in hours per week of all exercise-related activities, and duration in hours per week of moderate-vigorous exercise-related activities. The mean duration of all exercise-related activities and moderate-vigorous activities in hours per week are reported here for participants in each study arm who completed both the baseline and 12 week follow-up assessments. A higher mean indicates that a longer duration of exercise-related activities in hours per week were reported. |
| Quality of Life and Daily Function Questionnaires | baseline and through study completion an average of 12 weeks | Participants completed the Kansas City Cardiomyopathy questionnaire (KCCQ) and Duke Activity Status (DASI) Index standardized questionnaires. The KCCQ is scored on a scale of 0 to 100 with a higher score representing better health status. DASI is a 12-item questionnaire that is scored on a scale of 0 to 58.2, with a higher score representing a higher functional status. |
| Metabolomics | baseline and through study completion an average of 14 weeks | Nitric Oxide Bioavailability (uM) Metabolomics The scientific direction of our analyses for this measure has shifted over time. The investigators will pursue RNA seq and metabolomics to provide an unbiased path forward on viable targets in the muscle. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Inflammation - C-reactive Protein | baseline and through study completion an average of 14 weeks | Inflammation - C-reactive protein (CRP) will be measured through blood |
| Dual-energy X-ray Absorptiometry | Baseline and through study completion an average of 14 weeks | dual-energy x-ray absorptiometry will look at muscle mass change in kg |
Countries
United States
Participant flow
Pre-assignment details
65 participants consented to enroll in the study. 45 participants completed a baseline assessment and were randomized to one of the three intervention arms. The remaining 20 participants withdrew prior to completing baseline and before being randomized to one of the three intervention arms, so they are not included in this table. Serious adverse events reported after consent but prior to withdrawal for the non-randomized participants are included in a separate group in the adverse events table.
Participants by arm
| Arm | Count |
|---|---|
| Aerobic Exercise Intervention Participants completed a 12-week exercise training regimen consisting of aerobic exercise for a minimum of 60 minutes in length three times a week. | 16 |
| Combined Aerobic and Strength Exercise Intervention Participants completed a 12-week exercise training regimen consisting of combined aerobic and strength exercise for a minimum of 60 minutes in length three times a week. | 13 |
| Inspiratory Muscle Training Exercise Intervention Participants completed a 12-week exercise training regimen consisting of inspiratory muscle training exercise for a minimum of 60 minutes in length three times a week. | 12 |
| Consented But Withdrew Pre-randomization This group includes participants who consented to enroll in the study, but only completed partial or no baseline functional or questionnaire assessments, and then withdrew from the study prior to being randomized. Therefore these participants were not randomly assigned to one of the three study arms, but baseline demographic data were collected after consent and prior to randomization. The baseline demographic data are included here for completion. | 7 |
| Total | 48 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Lost to Follow-up | 1 | 2 | 0 |
| Overall Study | Withdrawal by Subject | 5 | 2 | 1 |
Baseline characteristics
| Characteristic | Aerobic Exercise Intervention | Total | Consented But Withdrew Pre-randomization | Inspiratory Muscle Training Exercise Intervention | Combined Aerobic and Strength Exercise Intervention |
|---|---|---|---|---|---|
| Age, Continuous | 70.1 years STANDARD_DEVIATION 7.5 | 69.7 years STANDARD_DEVIATION 7.7 | 70.7 years STANDARD_DEVIATION 9.8 | 69.2 years STANDARD_DEVIATION 5 | 67.6 years STANDARD_DEVIATION 7.9 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 5 Participants | 9 Participants | 0 Participants | 1 Participants | 3 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 4 Participants | 11 Participants | 6 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) White | 7 Participants | 28 Participants | 1 Participants | 10 Participants | 10 Participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 16 Participants | 48 Participants | 7 Participants | 12 Participants | 13 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 16 | 0 / 17 | 0 / 12 | 0 / 5 |
| other Total, other adverse events | 0 / 16 | 0 / 17 | 1 / 12 | 0 / 5 |
| serious Total, serious adverse events | 10 / 16 | 3 / 17 | 5 / 12 | 5 / 5 |
Outcome results
Primary
One Repetition Maximum- Leg Press
Leg press will be performed on the Keiser Leg press and measured in kilograms (kg)
Time frame: baseline and through study completion an average of 14 weeks
Population: Data available for 30 of 45 randomized participants who completed both a pre and post assessment.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Aerobic Exercise Intervention | One Repetition Maximum- Leg Press | 1 Rep Max Leg press follow-up | 433 kg | Standard Deviation 232.7 |
| Aerobic Exercise Intervention | One Repetition Maximum- Leg Press | 1 Rep Max Leg press baseline | 430.3 kg | Standard Deviation 208.6 |
| Combined Aerobic and Strength Exercise Intervention | One Repetition Maximum- Leg Press | 1 Rep Max Leg press baseline | 348.2 kg | Standard Deviation 143 |
| Combined Aerobic and Strength Exercise Intervention | One Repetition Maximum- Leg Press | 1 Rep Max Leg press follow-up | 355.5 kg | Standard Deviation 160.3 |
| Inspiratory Muscle Training Exercise Intervention | One Repetition Maximum- Leg Press | 1 Rep Max Leg press baseline | 421.1 kg | Standard Deviation 100.1 |
| Inspiratory Muscle Training Exercise Intervention | One Repetition Maximum- Leg Press | 1 Rep Max Leg press follow-up | 409.5 kg | Standard Deviation 136.4 |
Primary
Oxygen Uptake (VO2) Peak
a cardiopulmonary exercise test will be performed to determined peak VO2 in ML/KG/Min
Time frame: baseline and through study completion an average of 14 weeks
Population: Pre and post peak VO2 data available for 33 of 45 randomized participants. Remaining randomized participants did not complete a post assessment so are excluded from the table.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Aerobic Exercise Intervention | Oxygen Uptake (VO2) Peak | Baseline | 1778.1 ML/KG/Min | Standard Deviation 679.1 |
| Aerobic Exercise Intervention | Oxygen Uptake (VO2) Peak | Follow-up | 1763.6 ML/KG/Min | Standard Deviation 736.6 |
| Combined Aerobic and Strength Exercise Intervention | Oxygen Uptake (VO2) Peak | Baseline | 1228.2 ML/KG/Min | Standard Deviation 519.4 |
| Combined Aerobic and Strength Exercise Intervention | Oxygen Uptake (VO2) Peak | Follow-up | 1295.4 ML/KG/Min | Standard Deviation 499.4 |
| Inspiratory Muscle Training Exercise Intervention | Oxygen Uptake (VO2) Peak | Baseline | 1393.7 ML/KG/Min | Standard Deviation 305.3 |
| Inspiratory Muscle Training Exercise Intervention | Oxygen Uptake (VO2) Peak | Follow-up | 1405.9 ML/KG/Min | Standard Deviation 370.7 |
Secondary
Community Healthy Activities Model Program for Seniors (CHAMPS) Physical Activity Questionnaire for Older Adults - Duration Component
Participants completed the Community Healthy Activities Model Program for Seniors (CHAMPS) Physical Activity Questionnaire for Older Adults as part of the Quality of Life and Daily Function study outcome. The CHAMPS questionnaire assesses duration and frequency of self-reported weekly physical activities of varying intensities in older adults. One component of the CHAMPS score is the self-reported duration in hours per week of all exercise-related activities, and duration in hours per week of moderate-vigorous exercise-related activities. The mean duration of all exercise-related activities and moderate-vigorous activities in hours per week are reported here for participants in each study arm who completed both the baseline and 12 week follow-up assessments. A higher mean indicates that a longer duration of exercise-related activities in hours per week were reported.
Time frame: baseline and through study completion an average of 12 weeks
Population: Questionnaire data available for 32 participants who completed both the baseline and 12-week follow-up assessments. The mean at baseline and 12-week follow-up are reported.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Aerobic Exercise Intervention | Community Healthy Activities Model Program for Seniors (CHAMPS) Physical Activity Questionnaire for Older Adults - Duration Component | Baseline Mean Duration of all Physical Activity bouts (CHAMPS) | 15.2 hours per week | Standard Deviation 8.1 |
| Aerobic Exercise Intervention | Community Healthy Activities Model Program for Seniors (CHAMPS) Physical Activity Questionnaire for Older Adults - Duration Component | Follow-up Mean Duration of all Physical Activity bouts (CHAMPS) | 21.8 hours per week | Standard Deviation 15.9 |
| Aerobic Exercise Intervention | Community Healthy Activities Model Program for Seniors (CHAMPS) Physical Activity Questionnaire for Older Adults - Duration Component | Baseline Mean Duration of Moderate-Vigorous Physical Activity bouts (CHAMPS) | 6.8 hours per week | Standard Deviation 8.5 |
| Aerobic Exercise Intervention | Community Healthy Activities Model Program for Seniors (CHAMPS) Physical Activity Questionnaire for Older Adults - Duration Component | Follow-up Mean Duration of Moderate-Vigorous Physical Activity bouts (CHAMPS) | 11.6 hours per week | Standard Deviation 11.7 |
| Combined Aerobic and Strength Exercise Intervention | Community Healthy Activities Model Program for Seniors (CHAMPS) Physical Activity Questionnaire for Older Adults - Duration Component | Follow-up Mean Duration of Moderate-Vigorous Physical Activity bouts (CHAMPS) | 7.4 hours per week | Standard Deviation 6.2 |
| Combined Aerobic and Strength Exercise Intervention | Community Healthy Activities Model Program for Seniors (CHAMPS) Physical Activity Questionnaire for Older Adults - Duration Component | Baseline Mean Duration of all Physical Activity bouts (CHAMPS) | 7.7 hours per week | Standard Deviation 4.5 |
| Combined Aerobic and Strength Exercise Intervention | Community Healthy Activities Model Program for Seniors (CHAMPS) Physical Activity Questionnaire for Older Adults - Duration Component | Baseline Mean Duration of Moderate-Vigorous Physical Activity bouts (CHAMPS) | 3.5 hours per week | Standard Deviation 2.7 |
| Combined Aerobic and Strength Exercise Intervention | Community Healthy Activities Model Program for Seniors (CHAMPS) Physical Activity Questionnaire for Older Adults - Duration Component | Follow-up Mean Duration of all Physical Activity bouts (CHAMPS) | 14.3 hours per week | Standard Deviation 8.6 |
| Inspiratory Muscle Training Exercise Intervention | Community Healthy Activities Model Program for Seniors (CHAMPS) Physical Activity Questionnaire for Older Adults - Duration Component | Follow-up Mean Duration of Moderate-Vigorous Physical Activity bouts (CHAMPS) | 5.5 hours per week | Standard Deviation 5.4 |
| Inspiratory Muscle Training Exercise Intervention | Community Healthy Activities Model Program for Seniors (CHAMPS) Physical Activity Questionnaire for Older Adults - Duration Component | Follow-up Mean Duration of all Physical Activity bouts (CHAMPS) | 14.4 hours per week | Standard Deviation 9.6 |
| Inspiratory Muscle Training Exercise Intervention | Community Healthy Activities Model Program for Seniors (CHAMPS) Physical Activity Questionnaire for Older Adults - Duration Component | Baseline Mean Duration of Moderate-Vigorous Physical Activity bouts (CHAMPS) | 1.8 hours per week | Standard Deviation 1.9 |
| Inspiratory Muscle Training Exercise Intervention | Community Healthy Activities Model Program for Seniors (CHAMPS) Physical Activity Questionnaire for Older Adults - Duration Component | Baseline Mean Duration of all Physical Activity bouts (CHAMPS) | 5.7 hours per week | Standard Deviation 3.2 |
Secondary
Community Healthy Activities Model Program for Seniors (CHAMPS) Physical Activity Questionnaire for Older Adults - Frequency Component
Participants completed the Community Healthy Activities Model Program for Seniors (CHAMPS) Physical Activity Questionnaire for Older Adults as part of the Quality of Life and Daily Function study outcome. The CHAMPS questionnaire assesses duration and frequency of self-reported weekly physical activities of varying intensities in older adults. One component of the CHAMPS score is the frequency per week (i.e. number or count of events per week) that the participant reported that they engaged in all exercise related activities, and the frequency per week that the participant engaged in moderate-vigorous activities. The mean frequency of activities per week at baseline and follow-up for each study arm are reported here for the participants who completed both a baseline and follow-up assessment. A higher mean indicates a higher number of exercise-related activities were reported per week.
Time frame: baseline and through study completion an average of 12 weeks
Population: Questionnaire data available for 32 participants who completed both the baseline and 12-week follow-up assessments. The mean at baseline and 12-week follow-up are reported.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Aerobic Exercise Intervention | Community Healthy Activities Model Program for Seniors (CHAMPS) Physical Activity Questionnaire for Older Adults - Frequency Component | Baseline Mean Frequency of all Physical Activity bouts per week (CHAMPS) | 14.7 events per week | Standard Deviation 9.2 |
| Aerobic Exercise Intervention | Community Healthy Activities Model Program for Seniors (CHAMPS) Physical Activity Questionnaire for Older Adults - Frequency Component | Follow-up Mean Frequency of all Physical Activity bouts per week (CHAMPS) | 23.5 events per week | Standard Deviation 10.9 |
| Aerobic Exercise Intervention | Community Healthy Activities Model Program for Seniors (CHAMPS) Physical Activity Questionnaire for Older Adults - Frequency Component | Baseline Mean Frequency of Moderate-Vigorous Physical Activity bouts per week (CHAMPS) | 5.5 events per week | Standard Deviation 5.6 |
| Aerobic Exercise Intervention | Community Healthy Activities Model Program for Seniors (CHAMPS) Physical Activity Questionnaire for Older Adults - Frequency Component | Follow-up Mean Frequency of Moderate-Vigorous Physical Activity bouts per week (CHAMPS) | 12.1 events per week | Standard Deviation 8.1 |
| Combined Aerobic and Strength Exercise Intervention | Community Healthy Activities Model Program for Seniors (CHAMPS) Physical Activity Questionnaire for Older Adults - Frequency Component | Follow-up Mean Frequency of Moderate-Vigorous Physical Activity bouts per week (CHAMPS) | 10.6 events per week | Standard Deviation 6.7 |
| Combined Aerobic and Strength Exercise Intervention | Community Healthy Activities Model Program for Seniors (CHAMPS) Physical Activity Questionnaire for Older Adults - Frequency Component | Baseline Mean Frequency of all Physical Activity bouts per week (CHAMPS) | 13.6 events per week | Standard Deviation 9.3 |
| Combined Aerobic and Strength Exercise Intervention | Community Healthy Activities Model Program for Seniors (CHAMPS) Physical Activity Questionnaire for Older Adults - Frequency Component | Baseline Mean Frequency of Moderate-Vigorous Physical Activity bouts per week (CHAMPS) | 6.3 events per week | Standard Deviation 4.9 |
| Combined Aerobic and Strength Exercise Intervention | Community Healthy Activities Model Program for Seniors (CHAMPS) Physical Activity Questionnaire for Older Adults - Frequency Component | Follow-up Mean Frequency of all Physical Activity bouts per week (CHAMPS) | 22.5 events per week | Standard Deviation 11.8 |
| Inspiratory Muscle Training Exercise Intervention | Community Healthy Activities Model Program for Seniors (CHAMPS) Physical Activity Questionnaire for Older Adults - Frequency Component | Follow-up Mean Frequency of Moderate-Vigorous Physical Activity bouts per week (CHAMPS) | 7.7 events per week | Standard Deviation 4.9 |
| Inspiratory Muscle Training Exercise Intervention | Community Healthy Activities Model Program for Seniors (CHAMPS) Physical Activity Questionnaire for Older Adults - Frequency Component | Follow-up Mean Frequency of all Physical Activity bouts per week (CHAMPS) | 19.5 events per week | Standard Deviation 9.1 |
| Inspiratory Muscle Training Exercise Intervention | Community Healthy Activities Model Program for Seniors (CHAMPS) Physical Activity Questionnaire for Older Adults - Frequency Component | Baseline Mean Frequency of Moderate-Vigorous Physical Activity bouts per week (CHAMPS) | 3.0 events per week | Standard Deviation 2.9 |
| Inspiratory Muscle Training Exercise Intervention | Community Healthy Activities Model Program for Seniors (CHAMPS) Physical Activity Questionnaire for Older Adults - Frequency Component | Baseline Mean Frequency of all Physical Activity bouts per week (CHAMPS) | 9.5 events per week | Standard Deviation 4.2 |
Secondary
Metabolomics
Nitric Oxide Bioavailability (uM) Metabolomics The scientific direction of our analyses for this measure has shifted over time. The investigators will pursue RNA seq and metabolomics to provide an unbiased path forward on viable targets in the muscle.
Time frame: baseline and through study completion an average of 14 weeks
Population: Nitric oxide bioavailability metabolomics data were collected for 23 of the participants at both the baseline and follow-up assessments.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Aerobic Exercise Intervention | Metabolomics | Baseline Nitric Oxide (uM) | 6.2 micrometer (uM) | Standard Deviation 3.7 |
| Aerobic Exercise Intervention | Metabolomics | Follow-up Nitric Oxide (uM) | 5.6 micrometer (uM) | Standard Deviation 2.4 |
| Combined Aerobic and Strength Exercise Intervention | Metabolomics | Baseline Nitric Oxide (uM) | 7.7 micrometer (uM) | Standard Deviation 2.5 |
| Combined Aerobic and Strength Exercise Intervention | Metabolomics | Follow-up Nitric Oxide (uM) | 10.8 micrometer (uM) | Standard Deviation 8.9 |
| Inspiratory Muscle Training Exercise Intervention | Metabolomics | Follow-up Nitric Oxide (uM) | 6.6 micrometer (uM) | Standard Deviation 3.1 |
| Inspiratory Muscle Training Exercise Intervention | Metabolomics | Baseline Nitric Oxide (uM) | 7.2 micrometer (uM) | Standard Deviation 3.5 |
Secondary
Quality of Life and Daily Function Questionnaires
Participants completed the Kansas City Cardiomyopathy questionnaire (KCCQ) and Duke Activity Status (DASI) Index standardized questionnaires. The KCCQ is scored on a scale of 0 to 100 with a higher score representing better health status. DASI is a 12-item questionnaire that is scored on a scale of 0 to 58.2, with a higher score representing a higher functional status.
Time frame: baseline and through study completion an average of 12 weeks
Population: Questionnaire data available for 32 participants who completed both the baseline and 12-week follow-up assessments.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Aerobic Exercise Intervention | Quality of Life and Daily Function Questionnaires | KCCQ Baseline Score | 36 scores on a scale | Standard Deviation 10.6 |
| Aerobic Exercise Intervention | Quality of Life and Daily Function Questionnaires | KCCQ Follow-up Score | 40 scores on a scale | Standard Deviation 14 |
| Aerobic Exercise Intervention | Quality of Life and Daily Function Questionnaires | DASI Baseline Overall Score | 37.3 scores on a scale | Standard Deviation 14.6 |
| Aerobic Exercise Intervention | Quality of Life and Daily Function Questionnaires | DASI Follow-up Overall Score | 37.3 scores on a scale | Standard Deviation 15.2 |
| Combined Aerobic and Strength Exercise Intervention | Quality of Life and Daily Function Questionnaires | DASI Follow-up Overall Score | 32.9 scores on a scale | Standard Deviation 13 |
| Combined Aerobic and Strength Exercise Intervention | Quality of Life and Daily Function Questionnaires | KCCQ Baseline Score | 37.7 scores on a scale | Standard Deviation 12 |
| Combined Aerobic and Strength Exercise Intervention | Quality of Life and Daily Function Questionnaires | DASI Baseline Overall Score | 34.7 scores on a scale | Standard Deviation 15.4 |
| Combined Aerobic and Strength Exercise Intervention | Quality of Life and Daily Function Questionnaires | KCCQ Follow-up Score | 38 scores on a scale | Standard Deviation 13.2 |
| Inspiratory Muscle Training Exercise Intervention | Quality of Life and Daily Function Questionnaires | DASI Follow-up Overall Score | 33.4 scores on a scale | Standard Deviation 15.9 |
| Inspiratory Muscle Training Exercise Intervention | Quality of Life and Daily Function Questionnaires | KCCQ Follow-up Score | 43 scores on a scale | Standard Deviation 19.1 |
| Inspiratory Muscle Training Exercise Intervention | Quality of Life and Daily Function Questionnaires | DASI Baseline Overall Score | 33.4 scores on a scale | Standard Deviation 12.2 |
| Inspiratory Muscle Training Exercise Intervention | Quality of Life and Daily Function Questionnaires | KCCQ Baseline Score | 39.5 scores on a scale | Standard Deviation 16.2 |
Secondary
Skeletal Muscle Gene Expression
Skeletal muscle gene expression will be measured in RNA isolated from skeletal muscle biopsy samples via Illumina platform. The measure Number indicates the number of differentially expressed genes, and units are fold change over baseline. To investigate how the lifestyle interventions impacted gene expression at the mRNA level in skeletal muscles of our research participants we performed high-throughput RNA-Sequencing (Illumina HiSeq paired-end 150 base pairs). Differential gene expression analysis was performed on the RNA-seq. data using DeSEQ2 to determine differentially expressed genes (DEGs) between groups. All DEG analyses were performed using the Wald test (p \< 0.05) corrected for multiple comparisons using the Benjamini and Hochberg method.
Time frame: baseline and through study completion an average of 14 weeks
Population: Skeletal muscle samples were collected for 19 participants who completed both a baseline and follow-up assessment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Aerobic Exercise Intervention | Skeletal Muscle Gene Expression | 0 Fold change over baseline |
| Combined Aerobic and Strength Exercise Intervention | Skeletal Muscle Gene Expression | 1 Fold change over baseline |
| Inspiratory Muscle Training Exercise Intervention | Skeletal Muscle Gene Expression | 1 Fold change over baseline |
Other Pre-specified
Dual-energy X-ray Absorptiometry
dual-energy x-ray absorptiometry will look at muscle mass change in kg
Time frame: Baseline and through study completion an average of 14 weeks
Population: 23 randomized participants completed baseline dual-energy x-ray absorptiometry, and 15 of those completed the follow-up scan.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Aerobic Exercise Intervention | Dual-energy X-ray Absorptiometry | Appendicular Lean Mass Baseline | 3.96 kg | Standard Deviation 1.14 |
| Aerobic Exercise Intervention | Dual-energy X-ray Absorptiometry | Appendicular Lean Mass Follow-up | 8.73 kg | Standard Deviation 1.29 |
| Combined Aerobic and Strength Exercise Intervention | Dual-energy X-ray Absorptiometry | Appendicular Lean Mass Baseline | 3.08 kg | Standard Deviation 0.45 |
| Combined Aerobic and Strength Exercise Intervention | Dual-energy X-ray Absorptiometry | Appendicular Lean Mass Follow-up | 7.74 kg | Standard Deviation 1.28 |
| Inspiratory Muscle Training Exercise Intervention | Dual-energy X-ray Absorptiometry | Appendicular Lean Mass Follow-up | 7.72 kg | Standard Deviation 0.99 |
| Inspiratory Muscle Training Exercise Intervention | Dual-energy X-ray Absorptiometry | Appendicular Lean Mass Baseline | 3.08 kg | Standard Deviation 0.49 |
Other Pre-specified
Inflammation - C-reactive Protein
Inflammation - C-reactive protein (CRP) will be measured through blood
Time frame: baseline and through study completion an average of 14 weeks
Population: Data for the C-reactive protein outcome was collected for 28 participants.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Aerobic Exercise Intervention | Inflammation - C-reactive Protein | Baseline CRP (mg/L) | 3.3 mg/L | Standard Deviation 1.5 |
| Aerobic Exercise Intervention | Inflammation - C-reactive Protein | Follow-up CRP (mg/L) | 4.1 mg/L | Standard Deviation 4.1 |
| Combined Aerobic and Strength Exercise Intervention | Inflammation - C-reactive Protein | Baseline CRP (mg/L) | 3.8 mg/L | Standard Deviation 2.5 |
| Combined Aerobic and Strength Exercise Intervention | Inflammation - C-reactive Protein | Follow-up CRP (mg/L) | 4.2 mg/L | Standard Deviation 3.4 |
| Inspiratory Muscle Training Exercise Intervention | Inflammation - C-reactive Protein | Baseline CRP (mg/L) | 1.8 mg/L | Standard Deviation 1.6 |
| Inspiratory Muscle Training Exercise Intervention | Inflammation - C-reactive Protein | Follow-up CRP (mg/L) | 2.1 mg/L | Standard Deviation 2.1 |