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This is a research study being conducted to better understand the impact of exercise training on changes on the structure and function of the heart. Exercise training in patients with heart failure has been shown to be beneficial at decreasing symptoms of heart failure and improving overall functional capacity or capacity to exercise. However the mechanisms responsible for this are still unclear. This study will look specifically at how exercise creates changes within the hearts filling ability, the hearts pumping strength as well as the hearts ability to rebuild.
Prevalence of systolic heart failure (HF) is high among the growing population of older adults. Progressive cardiac remodeling and deteriorating cardiac output have been implicated as key factors underlying HF-related exercise intolerance and quality of life. Even after implementing medical and device therapies that moderate remodeling, exercise tolerance remains impaired. While exercise training has been demonstrated to improve exercise capacity, mechanisms facilitating this benefit remain unclear. Peripheral adaptations in the skeletal muscle and vasculature provide at least some benefit, however reverse cardiac remodeling (beyond effects of pharmacological and device therapies) may be additive. The investigators propose to study the impact of 2 different types of exercise on cardiac morphology as well as systolic and diastolic performance and related functional gains. The investigators will compare traditional aerobic training to a novel regimen of inspiratory muscle training (IMT). IMT is a specific type of exercise training that may be particularly useful for frail, infirmed HF patients who are unlikely to tolerate aerobic training. Effects of IMT on remodeling have not been previously studied.
The proposed echocardiography pilot study builds on a funded VA Merit F0834-R "Exercise Therapy to Reduce Heart Failure Symptoms; Sorting Mechanisms of Benefit" (Exercise therapy) PI, Forman that compares different modes of exercise training in older (age 50yrs) systolic (EF 45%) HF patients. The original study assesses peripheral mechanisms affected by exercise training, but was not designed to assess cardiac remodeling. The proposed pilot study provides a vital complementary analysis, i.e., it adds assessments of cardiac remodeling as well as related changes in systolic and diastolic performance.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| control | No Intervention | Will not receive intervention with exercise | |
| Intervention group | Active Comparator | 2 groups will receive 2 different types of therapy (exercise or Inspiratory Muscle Therapy) |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Exercise | Other | Exercise (walking 3 times a week for 60 minutes) or Inspiratory Muscle Therapy (breathing against an inspiratory resistive load 3 times a week for up to 60 minutes) |
| Measure | Description | Time Frame |
|---|---|---|
| Change in Left Ventricular Systolic Function. | Change in left ventricular ejection fraction. | Baseline and endpoint at 3-5 months |
| Change in Left Ventricular Structure. | Change in left ventricular mass. | Baseline and endpoint at 3-5 months |
| Change in Diastolic Function. | Change in mitral annular early diastolic velocity (e') | Baseline and endpoint at 3-5 months |
| Change in Left Ventricular (LV) Diastolic Function | Change in the ratio of early mitral in-flow velocity (E) to mitral annular early diastolic velocity (e') | Baseline and endpoint at 3-5 months |
| Change in Right Ventricular Function | Change in tricuspid annular tissue doppler velocity | Baseline and endpoint at 3-5 months |
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Inclusion Criteria:
In addition to the above we have now added patients with heart failure with preserved ejection fraction (similar to the parent study )pending Institutional Review Board (IRB) review.
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Jayashri Aragam, MD | VA Boston Healthcare System Jamaica Plain Campus, Jamaica Plain, MA | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| VA Boston Healthcare System Jamaica Plain Campus, Jamaica Plain, MA | Boston | Massachusetts | 02130 | United States |
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13 participants were consented but only 11 were enrolled. Two were excluded from randomization due to subsequent echocardiogram or pulmonary function screening not meeting enrollment criteria. One was withdrawn after enrollment due to increasing symptoms of heart failure.
Due to the small number of participants enrolled in each of the active intervention arms we combined participants from both intervention groups and analyzed against the controls.
Recruitment occurred at VA Boston Healthcare System cardiology related clinics from 6/6/2016 to 12/21/2018. As per the protocol the recruitment was supposed to begin in 2014. Unfortunately there were a number of issues including the fact that the parent study moved to Pittsburgh and we were not able to start recruitment till 2016.
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| ID | Title | Description |
|---|---|---|
| FG000 | Control | Will not receive intervention with exercise |
| FG001 | Intervention Group | 2 groups will receive 2 different types of exercise |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
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| ID | Title | Description |
|---|---|---|
| BG000 | Control | Will not receive intervention with exercise |
| BG001 | Intervention Group | 2 groups will receive 2 different types of exercise |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Change in Left Ventricular Systolic Function. | Change in left ventricular ejection fraction. | Posted | Mean | Standard Deviation | percent LVEF | Baseline and endpoint at 3-5 months |
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Adverse event data was collected while participants were enrolled from enrollment until collection of the final study endpoint at 3-5 months.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Control | Will not receive intervention with exercise | 0 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| ER Visit | Respiratory, thoracic and mediastinal disorders | Systematic Assessment | Patient had flu like symptoms and started coughing up blood. Patient treated with Tamiflu and sent home. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Not Fasted | General disorders | Systematic Assessment | Patient was not fasted at baseline visit. Patient completed fast blood draw on first day of intervention instead of during baseline visit. He confirmed he was fasted. |
Participation in this study hinged on recruitment into the parent study which was delayed due to various location and staff changes and early termination.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. Jayashri Aragam | VA Boston Healthcare System | 617-323-7700 | Jayashri.Aragam@va.gov |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| ICF | No | No | Yes | Informed Consent Form | Jul 13, 2015 | Oct 20, 2020 | ICF_000.pdf |
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Sep 20, 2017 | Nov 13, 2020 | Prot_SAP_001.pdf |
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| ID | Term |
|---|---|
| D006333 | Heart Failure |
| D009043 | Motor Activity |
| ID | Term |
|---|---|
| D006331 | Heart Diseases |
| D002318 | Cardiovascular Diseases |
| D001519 | Behavior |
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| ID | Term |
|---|---|
| D015444 | Exercise |
| ID | Term |
|---|---|
| D009043 | Motor Activity |
| D009068 | Movement |
| D009142 | Musculoskeletal Physiological Phenomena |
| D055687 | Musculoskeletal and Neural Physiological Phenomena |
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Non-randomized case control study with two groups. One group received exercise and the controls did not.
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| BG002 | Total | Total of all reporting groups |
| Participants |
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| Age, Continuous | Mean | Standard Deviation | years |
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| Sex: Female, Male | Count of Participants | Participants |
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| Race (NIH/OMB) | Count of Participants | Participants |
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| Region of Enrollment | Count of Participants | Participants |
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| Primary | Change in Left Ventricular Structure. | Change in left ventricular mass. | Posted | Mean | Standard Deviation | grams | Baseline and endpoint at 3-5 months |
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| Primary | Change in Diastolic Function. | Change in mitral annular early diastolic velocity (e') | Posted | Mean | Standard Deviation | centimeters/second | Baseline and endpoint at 3-5 months |
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| Primary | Change in Left Ventricular (LV) Diastolic Function | Change in the ratio of early mitral in-flow velocity (E) to mitral annular early diastolic velocity (e') | Posted | Mean | Standard Deviation | ratio | Baseline and endpoint at 3-5 months |
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| Primary | Change in Right Ventricular Function | Change in tricuspid annular tissue doppler velocity | Posted | Mean | Standard Deviation | centimeters/second | Baseline and endpoint at 3-5 months |
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| 5 |
| 0 |
| 5 |
| 0 |
| 5 |
| EG001 | Intervention Group | 2 groups will receive 2 different types of exercise | 0 | 5 | 4 | 5 | 1 | 5 |
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| HF exacerbation | Cardiac disorders | Systematic Assessment | Patient reported swelling and edema in legs. Reported to ER and was admitted. |
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| Low BP | Cardiac disorders | Systematic Assessment | Patient had low BP of 70/50 during a study visit. All other measures were in normal range. Had been taking additional diuretic and additional exercise. Patient was evaluated by cardiologist and sent home for dehydration. |
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| A-fib Hospitalization | Cardiac disorders | Systematic Assessment | Patient was admitted to non-VA hospital for A-fib. Treated with Amiodarone drip and cardioversion. |
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