Congenital Heart Disease, Single Ventricle
Conditions
Brief summary
Mechanisms that typically result in increased cardiac output, such as inotropic support, increased heart rate, and decreased afterload, have a blunted effect in Fontan circulation. The thoracic pump is a contributor to venous return that has been largely unexplored in patients with Fontan physiology. Inspiratory muscle training can improve the performance of competitive athletes across a range of sports and can improve quality of life and functional capacity in heart failure patients, presumably by reducing inspiratory muscle fatigue and possibly by improving peripheral blood flow during exercise. One could surmise that the effects of these changes would be particularly important in the Fontan population. The investigators propose to study the effects of inspiratory muscle training on exercise and pulmonary function parameters in a cohort of adult Fontan patients. The investigators hypothesize that a 12-week program of inspiratory muscle training with an inspiratory impedance threshold device will improve inspiratory muscle strength and endurance, and that this will translate into improved exercise performance in patients with Fontan physiology.
Interventions
DEVICETHRESHOLD(TM) INSPIRATORY MUSCLE TRAINER
Subjects will be provided with noseclips and a threshold impedance device set to 40% of their measured maximal inspiratory pressure and will be trained on using the device. Specifically, subjects will be instructed to breathe through the inspiratory muscle training device while wearing noseclips at a rate of 12 to 16 breaths per minute for 30 minutes a day, 5 days a week for 12 consecutive weeks. Each subject will be provided a customized schedule for increasing resistance by 2 cm H2O every 2 weeks to a maximum resistance of 41 cm H2O.
Sponsors
Boston Children's Hospital
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* 18 years of age and older * Fontan physiology * Undergoing cardiopulmonary stress testing * Able to complete a previous cardiopulmonary stress test in the preceding 24 months * Ability to comply with the inspiratory muscle training protocol * Ability to return for repeat stress testing and pulmonary function testing 12 weeks after enrollment * Ability to provide informed consent
Exclusion criteria
* Status post cardiac transplantation * Current pregnancy or plans to become pregnant within the next 3 months (for females of childbearing potential) * Active respiratory infection * Active cigarette smoker * Baseline oxygen saturation \<90% at the previous clinic visit or exercise test * Forced expired volume in 1 s and/or vital capacity \<60% of predicted at the previous exercise test * Cardiac surgery or catheter-based procedure in the preceding 18 months or planned surgery or catheter-based procedure within the next 3 months
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Change in Peak VO2 Between Baseline and Post-inspiratory Muscle Training Measurements. | Baseline and after 12 weeks of training |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in SF-36 Health Survey Score (Physical Component Summary) | 12 weeks | The 36-Item Short Form (SF-36) Health Survey is a disease-generic survey of an individual's perceived health status and health-related quality of life. There are eight scaled scores, which are the weighted sums of the questions in their section. Each scale is transformed into a 0-100 scale on the assumption that each question carries equal weight. The lower the score the more disability. The higher the score the less disability. These eight scales are then used to calculate (using a proprietary formula) two summary scores: the physical component score (PCS), representing the four physical health scales (physical functioning, role physical, bodily pain, general health), and the mental component score (MCS), representing the four mental health scales (mental health, role emotional, vitality, social functioning). Component scores are norm-based with a mean of 50 (standardized to the US population) and a standard deviation of 10. |
| Change in Innocor Measurement (Inert Gas Rebreathing Method) of Cardiac Output at Peak Exercise | 12 weeks | — |
Other
| Measure | Time frame |
|---|---|
| Change in Peak Work Rate During Exercise | Baseline and after 12 weeks of training |
| Change in VE/VCO2 Slope (Ratio) During Exercise | Baseline and after 12 weeks of training |
| Change in Maximum Voluntary Ventilation | 12 weeks |
| Change in Maximal Inspiratory Pressure | Baseline and after 12 weeks of training |
| Change in Oxygen Pulse at Peak Exercise | 12 weeks |
Countries
United States
Participant flow
Recruitment details
Consecutive adult patients (≥18years old) with Fontan physiology were recruited through the outpatient cardiology clinic at Boston Children's Hospital between April 2014 and December 2014.
Pre-assignment details
One subject who was enrolled and consented dropped out during the initial assessment due to inability to tolerate the metabolic cart during baseline exercise testing.
Participants by arm
| Arm | Count |
|---|---|
| THRESHOLD(TM) INSPIRATORY MUSCLE TRAINER THRESHOLD(TM) INSPIRATORY MUSCLE TRAINER: Subjects will be provided with noseclips and a threshold impedance device set to 40% of their measured maximal inspiratory pressure and will be trained on using the device. Specifically, subjects will be instructed to breathe through the inspiratory muscle training device while wearing noseclips at a rate of 12 to 16 breaths per minute for 30 minutes a day, 5 days a week for 12 consecutive weeks. Each subject will be provided a customized schedule for increasing resistance by 2 cm H2O every 2 weeks to a maximum resistance of 41 cm H2O. | 11 |
| Total | 11 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Withdrawal by Subject | 1 |
Baseline characteristics
| Characteristic | THRESHOLD(TM) INSPIRATORY MUSCLE TRAINER |
|---|---|
| Age at Fontan completion | 10.7 years STANDARD_DEVIATION 8 |
| Age, Continuous | 34.8 years STANDARD_DEVIATION 12.6 |
| Fontan type Atriopulmonary connection | 3 Participants |
| Fontan type Extracardiac conduit | 1 Participants |
| Fontan type Lateral tunnel | 7 Participants |
| Maximum inspiratory pressure | 87.7 cmH2O STANDARD_DEVIATION 33 |
| Peak heart rate | 132.3 beats per minute STANDARD_DEVIATION 31.8 |
| Peak relative VO2 | 68.1 % predicted STANDARD_DEVIATION 14.3 |
| Peak tidal volume | 2.03 L STANDARD_DEVIATION 0.58 |
| Peak VE | 74.3 L/min STANDARD_DEVIATION 27.8 |
| Peak work rate | 116.5 Watts STANDARD_DEVIATION 45 |
| Sex: Female, Male Female | 5 Participants |
| Sex: Female, Male Male | 6 Participants |
| VE/VCO2 slope (ratio) | 34.1 ratio STANDARD_DEVIATION 6.7 |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 11 |
| other Total, other adverse events | 0 / 11 |
| serious Total, serious adverse events | 0 / 11 |
Outcome results
Primary
Change in Peak VO2 Between Baseline and Post-inspiratory Muscle Training Measurements.
Time frame: Baseline and after 12 weeks of training
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| THRESHOLD(TM) INSPIRATORY MUSCLE TRAINER | Change in Peak VO2 Between Baseline and Post-inspiratory Muscle Training Measurements. | 24.0 ml/kg/min | Standard Deviation 9.8 |
p-value: 0.1673t-test, 2 sided
Secondary
Change in Innocor Measurement (Inert Gas Rebreathing Method) of Cardiac Output at Peak Exercise
Time frame: 12 weeks
Population: One individual failed to sustain maximal exercise long enough to complete measurement of cardiac output on her post-intervention study. That individual was therefore left out of the data analysis for cardiac output at peak exercise ONLY.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| THRESHOLD(TM) INSPIRATORY MUSCLE TRAINER | Change in Innocor Measurement (Inert Gas Rebreathing Method) of Cardiac Output at Peak Exercise | 6.8 L/min | Standard Deviation 1.9 |
p-value: 0.5745t-test, 2 sided
Secondary
Change in SF-36 Health Survey Score (Physical Component Summary)
The 36-Item Short Form (SF-36) Health Survey is a disease-generic survey of an individual's perceived health status and health-related quality of life. There are eight scaled scores, which are the weighted sums of the questions in their section. Each scale is transformed into a 0-100 scale on the assumption that each question carries equal weight. The lower the score the more disability. The higher the score the less disability. These eight scales are then used to calculate (using a proprietary formula) two summary scores: the physical component score (PCS), representing the four physical health scales (physical functioning, role physical, bodily pain, general health), and the mental component score (MCS), representing the four mental health scales (mental health, role emotional, vitality, social functioning). Component scores are norm-based with a mean of 50 (standardized to the US population) and a standard deviation of 10.
Time frame: 12 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| THRESHOLD(TM) INSPIRATORY MUSCLE TRAINER | Change in SF-36 Health Survey Score (Physical Component Summary) | 50.4 units on a scale | Standard Deviation 9.8 |
p-value: 0.511t-test, 2 sided
Other Pre-specified
Change in Maximal Inspiratory Pressure
Time frame: Baseline and after 12 weeks of training
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| THRESHOLD(TM) INSPIRATORY MUSCLE TRAINER | Change in Maximal Inspiratory Pressure | 96.0 cmH2O | Standard Deviation 33.1 |
p-value: 0.5374t-test, 2 sided
Other Pre-specified
Change in Maximum Voluntary Ventilation
Time frame: 12 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| THRESHOLD(TM) INSPIRATORY MUSCLE TRAINER | Change in Maximum Voluntary Ventilation | 113.4 L/min | Standard Deviation 31.5 |
p-value: 0.776t-test, 2 sided
Other Pre-specified
Change in Oxygen Pulse at Peak Exercise
Time frame: 12 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| THRESHOLD(TM) INSPIRATORY MUSCLE TRAINER | Change in Oxygen Pulse at Peak Exercise | 13.1 mL/beat | Standard Deviation 2.5 |
p-value: 0.3385t-test, 2 sided
Other Pre-specified
Change in Peak Work Rate During Exercise
Time frame: Baseline and after 12 weeks of training
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| THRESHOLD(TM) INSPIRATORY MUSCLE TRAINER | Change in Peak Work Rate During Exercise | 126.8 Watts | Standard Deviation 47 |
p-value: 0.0189t-test, 2 sided
Other Pre-specified
Change in VE/VCO2 Slope (Ratio) During Exercise
Time frame: Baseline and after 12 weeks of training
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| THRESHOLD(TM) INSPIRATORY MUSCLE TRAINER | Change in VE/VCO2 Slope (Ratio) During Exercise | 31.4 ratio | Standard Deviation 3.6 |
p-value: 0.1183t-test, 2 sided