Heart Failure, Sleep Apnea Syndromes
Conditions
Keywords
Heart Failure, Sleep Apnea, Ventricular Ejection Fraction, Exercise Test
Brief summary
The purpose of this study is to compare three treatment modalities for central, or mixed obstructive and central, sleep apnea in patients with chronic heart failure and reduced ejection fraction. The modalities to be tested are nocturnal supplemental oxygen (NSO) and continuous positive airway pressure (CPAP). The main outcome measures will be left ventricular ejection fraction on echocardiogram and peak oxygen consumption on cardiopulmonary exercise testing.
Detailed description
Chronic heart failure (HF) is a highly prevalent disease, with a lifetime risk of approximately 20%. Sleep apnea is a common co-morbid condition, occurring in approximately half of patients with chronic HF, and often has predominantly central or mixed obstructive and central characteristics. Although it is associated with increased mortality in patients with HF, sleep apnea is usually asymptomatic and patients are therefore often unwilling to accept standard therapy with positive airway pressure. At the outset of this study, there were three treatment modalities currently recommended by the American Academy of Sleep Medicine for the treatment of predominantly central sleep apnea in HF patients: nocturnal supplemental oxygen (NSO), continuous positive airway pressure (CPAP) and adaptive servo-ventilation (ASV). Recently, ASV was found to increase mortality in patients with heart failure with reduced ejection fraction and central sleep apnea. There are only limited data on the comparative efficacy and tolerability of these three modalities. The present study is designed to compare these modalities with respect to effects on ventricular function, exercise capacity, and other measures of cardiovascular risk.
Interventions
DEVICEContinuous positive airway pressure
Nocturnal continuous positive airway pressure, titrated to minimize apnea-hypopnea index
DEVICENocturnal supplemental oxygen
Nocturnal supplemental oxygen, titrated to 2-4 liters/minute with target of eliminating nocturnal hypoxemia
BEHAVIORALHealthy Lifestyle and Sleep Education
A 60-minute educational intervention with slide show and printed materials, educating the patient in healthy sleep habits and heart-healthy lifestyle
Sponsors
VA Office of Research and Development
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Outcomes Assessor)
Intervention model description
Continuous positive airway pressure (CPAP) and supplemental oxygen
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Veteran receiving care within the Veterans Health Administration healthcare system * Age 18 years * Physician diagnosis of chronic heart failure, American Heart Association Stage C-D * LVEF \<45% * No change in active cardiac medications for 4 weeks prior to randomization * Ability to provide informed consent * Moderate to severe central or mixed central and obstructive sleep apnea, defined as an apnea-hypopnea index (AHI) 15 events per hour, with a central AHI \>5 events/hour
Exclusion criteria
* Hospitalization for acute decompensated HF within previous 30 days * Hospitalization for myocardial infarction or cardiac surgery within previous 90 days * Presence of a left ventricular assist device * History of heart transplantation * Poorly controlled hypertension (\>170/\>110) * Poorly controlled diabetes (HbA1c \> 9.0) * Severe renal failure with estimated glomerular filtration rate \<30 ml/min * Prior stroke with functional impairment or other severe, uncontrolled medical problems that may impair ability to participate in the study exams, based on medical history and review of medical records * Severe chronic insomnia, with reported usual sleep duration \<4 hours * Severe daytime sleepiness, defined as Epworth Sleepiness Scale score 18 or higher or a report of falling asleep driving during the previous year, and deemed a safety risk by study physician * Awake resting oxyhemoglobin saturation \<89% * Pregnancy * Smoking by subject or other person in the subject's bedroom, or other open flame in bedroom * Current use of a positive airway pressure device (including continuous or bi-level positive airway pressure or adaptive servo-ventilation) or supplemental oxygen therapy
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Left Ventricular Ejection Fraction | 3 months | Standard transthoracic 2-dimensional and Doppler echocardiography will be performed. M-mode measurements of LV dimensions will be performed and analyzed according to the American Society of Echocardiography recommendations and LVEF measured using the modified Simpson's method. Measurement is change from baseline in LVEF. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Peak Oxygen Consumption (VO2 Peak) | 3 months | Treadmill exercise testing will be performed using a motor-driven treadmill and a modified Naughton protocol, with a lightweight disposable pneumotach device positioned in the participant's mouth interfaced with a metabolic cart. Change in VO2 peak between baseline and final visit will be the co-primary outcome of the study. Secondary outcome measures from cardiopulmonary exercise testing include VO2 at anaerobic threshold and VE/VCO2 slope. |
| 24-hour Ambulatory Blood Pressure | 3 months | 24-hour blood pressure will be measured using a blood pressure cuff that is connected by rubber tubing to a small pressure monitoring device, programmed to measure BP at 20 minute intervals during the day and 30 minute intervals at night (11 PM to 7 AM) for a period of 24 hours. The investigators will assess 24-hour mean arterial pressure as the primary blood pressure outcome, with additional assessment of nocturnal versus diurnal blood pressure effects. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| CPAP Nocturnal continuous positive airway pressure
Continuous positive airway pressure: Nocturnal continuous positive airway pressure, titrated to minimize apnea-hypopnea index
Healthy Lifestyle and Sleep Education: A 60-minute educational intervention with slide show and printed materials, educating the patient in healthy sleep habits and heart-healthy lifestyle | 31 |
| Oxygen Nocturnal supplemental oxygen
Nocturnal supplemental oxygen: Nocturnal supplemental oxygen, titrated to 2-4 liters/minute with target of eliminating nocturnal hypoxemia
Healthy Lifestyle and Sleep Education: A 60-minute educational intervention with slide show and printed materials, educating the patient in healthy sleep habits and heart-healthy lifestyle | 29 |
| HLSE Healthy lifestyle and sleep education control
Healthy Lifestyle and Sleep Education: A 60-minute educational intervention with slide show and printed materials, educating the patient in healthy sleep habits and heart-healthy lifestyle | 14 |
| Total | 74 |
Baseline characteristics
| Characteristic | CPAP | Oxygen | HLSE | Total |
|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 26 Participants | 24 Participants | 10 Participants | 60 Participants |
| Age, Categorical Between 18 and 65 years | 5 Participants | 5 Participants | 4 Participants | 14 Participants |
| Age, Continuous | 72.7 years STANDARD_DEVIATION 10.2 | 71.7 years STANDARD_DEVIATION 8.3 | 70.5 years STANDARD_DEVIATION 8.1 | 71.9 years STANDARD_DEVIATION 9.1 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants | 2 Participants | 0 Participants | 4 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 27 Participants | 25 Participants | 13 Participants | 65 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 2 Participants | 2 Participants | 1 Participants | 5 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants | 4 Participants | 2 Participants | 8 Participants |
| Race (NIH/OMB) More than one race | 2 Participants | 0 Participants | 0 Participants | 2 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 3 Participants | 3 Participants | 0 Participants | 6 Participants |
| Race (NIH/OMB) White | 23 Participants | 22 Participants | 12 Participants | 57 Participants |
| Sex: Female, Male Female | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Sex: Female, Male Male | 31 Participants | 28 Participants | 14 Participants | 73 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 31 | 0 / 29 | 0 / 14 |
| other Total, other adverse events | 10 / 31 | 13 / 29 | 4 / 14 |
| serious Total, serious adverse events | 4 / 31 | 4 / 29 | 2 / 14 |
Outcome results
Primary
Left Ventricular Ejection Fraction
Standard transthoracic 2-dimensional and Doppler echocardiography will be performed. M-mode measurements of LV dimensions will be performed and analyzed according to the American Society of Echocardiography recommendations and LVEF measured using the modified Simpson's method. Measurement is change from baseline in LVEF.
Time frame: 3 months
Population: All participants with both baseline and follow-up echocardiograms. There were 5 dropouts from the CPAP group, 2 from the NSO group and 1 from the HLSE group.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| CPAP | Left Ventricular Ejection Fraction | 1.63 percent of LV diastolic volume | Standard Deviation 4.88 |
| Oxygen | Left Ventricular Ejection Fraction | 1.69 percent of LV diastolic volume | Standard Deviation 8.33 |
| HLSE | Left Ventricular Ejection Fraction | 4.42 percent of LV diastolic volume | Standard Deviation 4.85 |
Secondary
24-hour Ambulatory Blood Pressure
24-hour blood pressure will be measured using a blood pressure cuff that is connected by rubber tubing to a small pressure monitoring device, programmed to measure BP at 20 minute intervals during the day and 30 minute intervals at night (11 PM to 7 AM) for a period of 24 hours. The investigators will assess 24-hour mean arterial pressure as the primary blood pressure outcome, with additional assessment of nocturnal versus diurnal blood pressure effects.
Time frame: 3 months
Population: Participants completing 24-hour ambulatory BP monitoring at final visit
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| CPAP | 24-hour Ambulatory Blood Pressure | 87.5 torr | Standard Deviation 8.5 |
| Oxygen | 24-hour Ambulatory Blood Pressure | 88.0 torr | Standard Deviation 9.1 |
| HLSE | 24-hour Ambulatory Blood Pressure | 77.4 torr | Standard Deviation 9.9 |
Secondary
Peak Oxygen Consumption (VO2 Peak)
Treadmill exercise testing will be performed using a motor-driven treadmill and a modified Naughton protocol, with a lightweight disposable pneumotach device positioned in the participant's mouth interfaced with a metabolic cart. Change in VO2 peak between baseline and final visit will be the co-primary outcome of the study. Secondary outcome measures from cardiopulmonary exercise testing include VO2 at anaerobic threshold and VE/VCO2 slope.
Time frame: 3 months
Population: All randomized participants completing baseline and follow-up cardiopulmonary exercise testing
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| CPAP | Peak Oxygen Consumption (VO2 Peak) | -0.40 ml/kg/min | Standard Deviation 2.59 |
| Oxygen | Peak Oxygen Consumption (VO2 Peak) | 0.11 ml/kg/min | Standard Deviation 4.75 |
| HLSE | Peak Oxygen Consumption (VO2 Peak) | -1.54 ml/kg/min | Standard Deviation 2.39 |