Acute Decompensated Heart Failure, Sleep Disordered Breathing
Conditions
Keywords
heart failure, congestive heart failure, acute decompensated heart failure, chronic heart failure, left-sided heart failure, heart failure decompensation, sleep apnea, sleep disordered breathing, central sleep apnea, obstructive sleep apnea, cheyne-stokes respiration
Brief summary
The aim of the study is to compare the effects of MV targeted ASV in addition to optimized medical therapy versus optimized medical therapy alone at 6 months in patients with acute decompensated HF. The study will also assess changes in functional parameters, biomarkers, quality of life (QOL), and sleep.
Detailed description
This study is a randomized, unblinded, multi-center trial with parallel group design, with subjects randomized to either control (optimized medical therapy for chronic heart failure) or active treatment (optimized medical therapy plus use of MV-targeted ASV) in a 1:1 ratio.
Interventions
DEVICEMV ASV
Minute ventilation-targeted servo-ventilation therapy.
Beta Blockers, ACE inhibitor or ARB, loop diuretics and/or spironolactone as appropriate, statin if indicated, aspirin and/or warfarin if indicated
Sponsors
ResMed Foundation
ResMed
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
SUPPORTIVE_CARE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
21 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Patients 21 years or older * Patients with prior clinical diagnosis of heart failure (HFrEF or HFpEF), or de novo diagnosis of HFpEF indicated by a local BNP≥300 pg/mL or NT pro-BNP≥1200 pg/mL on admission without systolic blood pressure \>180 mmHg or atrial fibrillation, or diagnosis of HFrEF indicated by documented evidence of prescribed beta-blockers and ACE-inhibitors or ARBs for at least 4 weeks prior to admission * Hospital admission for acute decompensated HF as determined by: * Dyspnea at rest or with minimal exertion * AND At least two of the following signs and symptoms: * Orthopnea * Pulmonary rales beyond basilar * Chest congestion on x-ray * BNP≥300pg/mL or NT pro-BNP≥1200pg/mL * Pulmonary capillary wedge pressure (PCWP) ≥25mmHg during current hospitalization * Presented to hospital or clinic at least 24 hours prior to consent * Patient stable enough to stop oxygen use for duration of polygraphy test or have access to dual lumen cannula for polygraphy test * Sleep disordered breathing (SDB) documented by polygraphy with an AHI≥15 events/hour * Patient is able to fully understand study information and sign a consent form
Exclusion criteria
* Right-sided heart failure without left-sided heart failure * Sustained systolic blood pressure \<80 mmHg at baseline * Acute coronary syndrome within 1 months of randomization * Active myocarditis * Complex congenital heart disease * Constrictive pericarditis * Non-cardiac pulmonary edema * Clinical evidence of digoxin toxicity * Need for mechanical hemodynamic support at time of randomization * Oxygen saturation ≤85% at rest during the day or at start of nocturnal oximetry recording or regular use of oxygen therapy (day or night) * COPD exacerbation as the primary reason for hospital admission * Current use (within 4 weeks of study entry) of any PAP-therapy (eg, fixed, bi-level, or APAP) * Life expectancy \< 1 year for diseases unrelated to HF * Transient ischemic attack (TIA) or Stroke within 3 months prior to randomization * CABG procedure within 3 months prior to randomization, or planned to occur during study period * CRT implant within 3 months prior to randomization , or planned to occur during study period * VAD implant planned to occur during study period * Heart transplant list Status 1a or 1b * Status post-transplant or LVAD * Prescribed inotrope therapy anticipated at discharge * Chronic Dialysis * Known amyloidosis, hypertrophic obstructive cardiomyopathy, arteriovenous fistulas * Primary hemodynamically significant uncorrected valvular heart disease (obstructive or regurgitant) with planned intervention within 6 months of randomization * Pregnant, or planning to become pregnant * Cannot tolerate ASV treatment during run-in * Cannot perform 6MWT at baseline * Occupation as a commercial driver or pilot and plan to be performing these activities during the study period * Inability to comply with planned study procedures * Participation in pharmaceutical or treatment-related clinical study within 1 month of study enrollment
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Global Rank Endpoint | Baseline, 6 months | A rank order response based on survival free from CV hospitalization and improvement in functional capacity measured by 6MWD. All participants were first ranked by time to death, then ranked by time to CV hospitalization, and then ranked by percentage change in 6MWD. For time to event measures (time to death and time to hospitalization), the shorter the amount of time, the lower the rank assigned to that participant. For percentage changes in 6MWD, the smaller the percentage change, the lower the rank assigned to that participant. Each component was then combined to create a rank value that ranged between 0 and 100. Overall, higher rank values are associated with better outcomes. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| NT Pro-BNP | Change from Baseline to 6 months | Change in neurohumoral activation as measured by N-terminal pro b-type natriuretic peptide. |
| Kansas City Cardiomyopathy Questionnaire (KCCQ) | Change from Baseline to 6 months | The KCCQ is a 23-item, self-administered instrument that quantifies physical function, symptoms (frequency, severity and recent change), social function, self-efficacy and knowledge, and quality of life. Scores are transformed to a range of 0-100, in which higher scores reflect better health status. |
| Biomarkers - Inflammation | Change from Baseline to 6 months | Biomarkers of inflammation reported as troponin I ultra-sensitive |
| Biomarkers - Cardiovascular | Change from Baseline to 6 months | Biomarkers of cardiovascular function reported as hs-CRP |
| Biomarkers - Renal Function | Change from Baseline to 6 months | Biomarkers of renal function reported as creatinine |
| ECHO Parameters - LVEF | Change from Baseline to 6 months | Echocardiographic parameters, including LVEF (left ventricular ejection fraction) and LVESVI (left ventricular end-systolic volume index) for patients with HFrEF (heart failure with reduced ejection fraction), and E/e' (ratio between early mitral inflow velocity and mitral annular early diastolic velocity) for patients with HFrEF or HFpEF (heart failure with preserved ejection fraction). |
| ECHO Parameters - LVESVI | Change from Baseline to 6 months | Echocardiographic parameters, including LVEF (left ventricular ejection fraction) and LVESVI (left ventricular end-systolic volume index) for patients with HFrEF (heart failure with reduced ejection fraction), and E/e' (ratio between early mitral inflow velocity and mitral annular early diastolic velocity) for patients with HFrEF or HFpEF (heart failure with preserved ejection fraction). |
| ECHO Parameters - E/e' Ratio | Change from Baseline to 6 months | Echocardiographic parameters, including LVEF (left ventricular ejection fraction) and LVESVI (left ventricular end-systolic volume index) for patients with HFrEF (heart failure with reduced ejection fraction), and E/e' (ratio between early mitral inflow velocity and mitral annular early diastolic velocity) for patients with HFpEF (heart failure with preserved ejection fraction). |
| Win Ratio | 6 months | Patients in the new treatment and control groups are formed into matched pairs based on their risk profiles. For each matched pair, the new treatment patient is labeled a 'winner' or a 'loser' depending on who had a CV death first. If that is not known, they are labeled a 'winner' or 'loser' depending on who had a HF hospitalization first. Otherwise they are considered tied. The win ratio is the total number of winners divided by the total numbers of losers. |
| Six-minute Walk Distance | Change from Baseline to 6 months | Change in functional parameters as measured by 6-minute walk test (6MWT) |
| Number of Subjects With HF Hospitalization | 2 days, 1 week, 1, 2, 3, and 6 months | Rates of hospitalization or urgent clinic visit for worsening of heart failure and for any reason |
| Death | 2 days, 1 week, 1, 2, 3, and 6 months | Rate of Cardiovascular and all-cause death |
| Time Dead/Hospitalized | 6 months | Total days dead or hospitalized at study end |
| DASI | Change from Baseline to 6 months | The Duke Activity Status Index is a 12-item patient-reported outcome validated for the assessment of functional capacity based on the ability to perform everyday activities. With a total range of 0 to 58.20, a higher score indicates better quality of life. |
| EQ-5D-5L Index | Change from Baseline to 6 months | The EQ-5D-5L is a standardized self-report questionnaire that is used as a measure of health outcome. The EQ-5D-5L questionnaire is comprised of the following 5 dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension has 5 levels: no problems, slight problems, moderate problems, severe problems, and extreme problems. Responses were indexed using the EQ-5D-5L US value set to scale the 5 dimensions. A score of -0.109 indicates extreme problems for all dimensions and a score of 1.000 indicates no problems for all dimensions. Therefore, a higher score indicates better general health. |
| PHQ-9 | Change from Baseline to 6 months | The PHQ-9 is the nine item depression scale of the Patient Health Questionnaire. The PHQ-9 is a self-administered instrument for screening, diagnosing, monitoring and measuring the severity of depression. The PHQ-9 incorporates DSM-IV depression diagnostic criteria with other leading major depressive symptoms into a brief self-report tool. The tool rates the frequency of the symptoms which factors into the following scoring severity index: 0 - Not at all, 1 - Several Days, 2 - More than Half the Days, 3 - Nearly Every Day. Total score can range from 0 to 27. A higher score indicates increased severity. |
| PSQI | Change from Baseline to 6 months | The Pittsburgh Sleep Quality Index is a 19-item subjective measurement of sleep. It is an effective instrument used to measure the quality and patterns of sleep in the older adult. It differentiates poor from good sleep by measuring seven areas: subjective sleep quality, sleep latency, sleep duration, habitual sleep efficiency, sleep disturbances, use of sleeping medication and daytime dysfunction over the last month. The subject self-rates each of these seven areas of sleep. The seven component scores are then added to yield a total score with a range of 0-21 points, 0 indicating no difficulty and 21 indicating severe difficulties in all areas. |
| ESS | Change from Baseline to 6 months | The Epworth Sleepiness Scale is a simple, 8-item self-administered questionnaire which provides a measurement of the subject's general level of daytime sleepiness. The individual is asked on a scale of 0-3 to score the likelihood of falling asleep in eight various situations. With a total range of 0 to 24, a higher score indicates increased severity. |
| Sleep Parameters | Change from Baseline to 6 months | Sleep and sleep disordered breathing parameters (AHI, nocturnal hypoxemia) |
Countries
Germany, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| MV ASV+OMT Minute Ventilation-targeted adaptive servo-ventilation therapy plus optimized medical treatment
MV ASV: Minute ventilation-targeted servo-ventilation therapy.
Optimized Medical Treatment: Beta Blockers, ACE inhibitor or ARB, loop diuretics and/or spironolactone as appropriate, statin if indicated, aspirin and/or warfarin if indicated | 65 |
| OMT Only Optimized Medical Treatment for heart failure in accordance with applicable guidelines (ACCF/AHA Guideline for the Management of Heart Failure and HFSA Heart Failure Guidelines.
Optimized Medical Treatment: Beta Blockers, ACE inhibitor or ARB, loop diuretics and/or spironolactone as appropriate, statin if indicated, aspirin and/or warfarin if indicated | 61 |
| Total | 126 |
Baseline characteristics
| Characteristic | OMT Only | MV ASV+OMT | Total |
|---|---|---|---|
| 6-minute walk distance | 196.1 meters STANDARD_DEVIATION 114.6 | 221.4 meters STANDARD_DEVIATION 122.7 | 209.2 meters STANDARD_DEVIATION 119 |
| Age, Continuous | 63.2 years STANDARD_DEVIATION 13.4 | 61.1 years STANDARD_DEVIATION 13.5 | 62.1 years STANDARD_DEVIATION 13.4 |
| Atrial fibrillation | 26 participants | 26 participants | 52 participants |
| Body mass index | 31.4 kg/m^2 STANDARD_DEVIATION 8.6 | 32.3 kg/m^2 STANDARD_DEVIATION 9 | 31.9 kg/m^2 STANDARD_DEVIATION 8.8 |
| Comorbid Conditions COPD | 11 participants | 12 participants | 23 participants |
| Comorbid Conditions Diabetes mellitus | 34 participants | 35 participants | 69 participants |
| Comorbid Conditions Hypertension | 56 participants | 52 participants | 108 participants |
| Concomitant medications ACE-I or ARB (HFrEF only) | 38 participants | 39 participants | 77 participants |
| Concomitant medications Aldosterone agonist | 29 participants | 33 participants | 62 participants |
| Concomitant medications Beta blocker (HFrEF only) | 46 participants | 47 participants | 93 participants |
| Concomitant medications Loop diuretic | 53 participants | 58 participants | 111 participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 4 Participants | 4 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 60 Participants | 59 Participants | 119 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants | 2 Participants | 3 Participants |
| Implanted device ICD | 15 participants | 26 participants | 41 participants |
| Implanted device Pacemaker | 6 participants | 3 participants | 9 participants |
| Ischemic HF etiology | 18 participants | 26 participants | 44 participants |
| Left ventricular ejection fraction (LVEF) Preserved ejection fraction (>45%) | 11 Participants | 13 Participants | 24 Participants |
| Left ventricular ejection fraction (LVEF) Reduced ejection fraction (</=45%) | 50 Participants | 52 Participants | 102 Participants |
| New York Heart Association (NYHA) Class Not done | 1 Participants | 2 Participants | 3 Participants |
| New York Heart Association (NYHA) Class NYHA Class I | 3 Participants | 3 Participants | 6 Participants |
| New York Heart Association (NYHA) Class NYHA Class II | 11 Participants | 19 Participants | 30 Participants |
| New York Heart Association (NYHA) Class NYHA Class III | 43 Participants | 32 Participants | 75 Participants |
| New York Heart Association (NYHA) Class NYHA Class IV | 3 Participants | 9 Participants | 12 Participants |
| N-terminal pro-brain natriuretic peptide (NT pro-BNP) | 6056.4 pg/mL STANDARD_DEVIATION 8401.9 | 3468.5 pg/mL STANDARD_DEVIATION 4231.6 | 4752.0 pg/mL STANDARD_DEVIATION 6734.9 |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 3 Participants | 0 Participants | 3 Participants |
| Race (NIH/OMB) Black or African American | 23 Participants | 28 Participants | 51 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 1 Participants | 1 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 | 1 Participants | 1 Participants |
| Race (NIH/OMB) White | 34 Participants | 35 Participants | 69 Participants |
| Region of Enrollment Germany | 18 participants | 17 participants | 35 participants |
| Region of Enrollment United States | 43 participants | 48 participants | 91 participants |
| Sex: Female, Male Female | 17 Participants | 16 Participants | 33 Participants |
| Sex: Female, Male Male | 44 Participants | 49 Participants | 93 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 4 / 65 | 7 / 61 |
| other Total, other adverse events | 2 / 58 | 1 / 61 |
| serious Total, serious adverse events | 0 / 65 | 0 / 61 |
Outcome results
Primary
Global Rank Endpoint
A rank order response based on survival free from CV hospitalization and improvement in functional capacity measured by 6MWD. All participants were first ranked by time to death, then ranked by time to CV hospitalization, and then ranked by percentage change in 6MWD. For time to event measures (time to death and time to hospitalization), the shorter the amount of time, the lower the rank assigned to that participant. For percentage changes in 6MWD, the smaller the percentage change, the lower the rank assigned to that participant. Each component was then combined to create a rank value that ranged between 0 and 100. Overall, higher rank values are associated with better outcomes.
Time frame: Baseline, 6 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| MV ASV+OMT | Global Rank Endpoint | 50.4 Standardized global rank order value | Standard Deviation 28.3 |
| OMT Only | Global Rank Endpoint | 49.6 Standardized global rank order value | Standard Deviation 30 |
Comparison: The primary endpoint was a composite measure of global rank order response based on survival time, freedom from CV hospitalization, and improvement in functional capacity measured by percent change in 6MWD from baseline to 6 months. The plan was to randomize up to 215 subjects. However, due to safety issues observed in SERVE-HF, randomization was stopped at 126 subjects.p-value: 0.916Wilcoxon (Mann-Whitney)
Secondary
Biomarkers - Cardiovascular
Biomarkers of cardiovascular function reported as hs-CRP
Time frame: Change from Baseline to 6 months
Population: Not all participants had biomarker samples that were able to be analyzed. For endpoints that needed a change in measures from baseline to 6 months, if a subject missed one of the measurements, the subject was excluded from the analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| MV ASV+OMT | Biomarkers - Cardiovascular | 0.03 mg/L | Standard Deviation 0.6 |
| OMT Only | Biomarkers - Cardiovascular | 0.29 mg/L | Standard Deviation 1.6 |
Secondary
Biomarkers - Inflammation
Biomarkers of inflammation reported as troponin I ultra-sensitive
Time frame: Change from Baseline to 6 months
Population: Not all participants had biomarker samples that were able to be analyzed. For endpoints that needed a change in measures from baseline to 6 months, if a subject missed one of the measurements, the subject was excluded from the analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| MV ASV+OMT | Biomarkers - Inflammation | -13.3 ng/mL | Standard Deviation 32.1 |
| OMT Only | Biomarkers - Inflammation | -14.1 ng/mL | Standard Deviation 41.8 |
Secondary
Biomarkers - Renal Function
Biomarkers of renal function reported as creatinine
Time frame: Change from Baseline to 6 months
Population: Not all participants had biomarker samples that were able to be analyzed. For endpoints that needed a change in measures from baseline to 6 months, if a subject missed one of the measurements, the subject was excluded from the analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| MV ASV+OMT | Biomarkers - Renal Function | 0.18 mg/dL | Standard Deviation 0.66 |
| OMT Only | Biomarkers - Renal Function | 0.08 mg/dL | Standard Deviation 0.38 |
Secondary
DASI
The Duke Activity Status Index is a 12-item patient-reported outcome validated for the assessment of functional capacity based on the ability to perform everyday activities. With a total range of 0 to 58.20, a higher score indicates better quality of life.
Time frame: Change from Baseline to 6 months
Population: For endpoints that needed a change in measures from baseline to 6 months, if a subject missed one of the measurements, the subject was excluded from the analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| MV ASV+OMT | DASI | 3.7 scores on a scale | Standard Deviation 13.4 |
| OMT Only | DASI | 5.2 scores on a scale | Standard Deviation 14.5 |
Secondary
Death
Rate of Cardiovascular and all-cause death
Time frame: 2 days, 1 week, 1, 2, 3, and 6 months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| MV ASV+OMT | Death | 4 Participants |
| OMT Only | Death | 7 Participants |
Secondary
ECHO Parameters - E/e' Ratio
Echocardiographic parameters, including LVEF (left ventricular ejection fraction) and LVESVI (left ventricular end-systolic volume index) for patients with HFrEF (heart failure with reduced ejection fraction), and E/e' (ratio between early mitral inflow velocity and mitral annular early diastolic velocity) for patients with HFpEF (heart failure with preserved ejection fraction).
Time frame: Change from Baseline to 6 months
Population: For endpoints that needed a change in measures from baseline to 6 months, if a subject missed one of the measurements, the subject was excluded from the analysis. HFrEF and HFpEF subjects were separated accordingly.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| MV ASV+OMT | ECHO Parameters - E/e' Ratio | Change in E/e' (HFpEF) | -2.1 ratio | Standard Deviation 9 |
| MV ASV+OMT | ECHO Parameters - E/e' Ratio | Change in E/e' (HFrEF) | -3.2 ratio | Standard Deviation 9.6 |
| OMT Only | ECHO Parameters - E/e' Ratio | Change in E/e' (HFpEF) | -4.6 ratio | Standard Deviation 6.7 |
| OMT Only | ECHO Parameters - E/e' Ratio | Change in E/e' (HFrEF) | -2.6 ratio | Standard Deviation 13.7 |
Secondary
ECHO Parameters - LVEF
Echocardiographic parameters, including LVEF (left ventricular ejection fraction) and LVESVI (left ventricular end-systolic volume index) for patients with HFrEF (heart failure with reduced ejection fraction), and E/e' (ratio between early mitral inflow velocity and mitral annular early diastolic velocity) for patients with HFrEF or HFpEF (heart failure with preserved ejection fraction).
Time frame: Change from Baseline to 6 months
Population: For endpoints that needed a change in measures from baseline to 6 months, if a subject missed one of the measurements, the subject was excluded from the analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| MV ASV+OMT | ECHO Parameters - LVEF | 3.8 %EF | Standard Deviation 6.3 |
| OMT Only | ECHO Parameters - LVEF | 5.0 %EF | Standard Deviation 9.5 |
Secondary
ECHO Parameters - LVESVI
Echocardiographic parameters, including LVEF (left ventricular ejection fraction) and LVESVI (left ventricular end-systolic volume index) for patients with HFrEF (heart failure with reduced ejection fraction), and E/e' (ratio between early mitral inflow velocity and mitral annular early diastolic velocity) for patients with HFrEF or HFpEF (heart failure with preserved ejection fraction).
Time frame: Change from Baseline to 6 months
Population: For endpoints that needed a change in measures from baseline to 6 months, if a subject missed one of the measurements, the subject was excluded from the analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| MV ASV+OMT | ECHO Parameters - LVESVI | -9.0 mL/m^2 | Standard Deviation 21.1 |
| OMT Only | ECHO Parameters - LVESVI | -8.6 mL/m^2 | Standard Deviation 16.2 |
Secondary
EQ-5D-5L Index
The EQ-5D-5L is a standardized self-report questionnaire that is used as a measure of health outcome. The EQ-5D-5L questionnaire is comprised of the following 5 dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension has 5 levels: no problems, slight problems, moderate problems, severe problems, and extreme problems. Responses were indexed using the EQ-5D-5L US value set to scale the 5 dimensions. A score of -0.109 indicates extreme problems for all dimensions and a score of 1.000 indicates no problems for all dimensions. Therefore, a higher score indicates better general health.
Time frame: Change from Baseline to 6 months
Population: For endpoints that needed a change in measures from baseline to 6 months, if a subject missed one of the measurements, the subject was excluded from the analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| MV ASV+OMT | EQ-5D-5L Index | 0.07 scores on a scale | Standard Deviation 0.23 |
| OMT Only | EQ-5D-5L Index | 0.03 scores on a scale | Standard Deviation 0.22 |
Secondary
ESS
The Epworth Sleepiness Scale is a simple, 8-item self-administered questionnaire which provides a measurement of the subject's general level of daytime sleepiness. The individual is asked on a scale of 0-3 to score the likelihood of falling asleep in eight various situations. With a total range of 0 to 24, a higher score indicates increased severity.
Time frame: Change from Baseline to 6 months
Population: For endpoints that needed a change in measures from baseline to 6 months, if a subject missed one of the measurements, the subject was excluded from the analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| MV ASV+OMT | ESS | -1.6 scores on a scale | Standard Deviation 5.6 |
| OMT Only | ESS | -2.1 scores on a scale | Standard Deviation 5.1 |
Secondary
Kansas City Cardiomyopathy Questionnaire (KCCQ)
The KCCQ is a 23-item, self-administered instrument that quantifies physical function, symptoms (frequency, severity and recent change), social function, self-efficacy and knowledge, and quality of life. Scores are transformed to a range of 0-100, in which higher scores reflect better health status.
Time frame: Change from Baseline to 6 months
Population: For endpoints that needed a change in measures from baseline to 6 months, if a subject missed one of the measurements, the subject was excluded from the analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| MV ASV+OMT | Kansas City Cardiomyopathy Questionnaire (KCCQ) | 20.3 scores on a scale | Standard Deviation 28.3 |
| OMT Only | Kansas City Cardiomyopathy Questionnaire (KCCQ) | 24.7 scores on a scale | Standard Deviation 28 |
Secondary
NT Pro-BNP
Change in neurohumoral activation as measured by N-terminal pro b-type natriuretic peptide.
Time frame: Change from Baseline to 6 months
Population: For endpoints that needed a change in measures from baseline to 6 months, if a subject missed one of the measurements, the subject was excluded from the analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| MV ASV+OMT | NT Pro-BNP | 172.7 pg/mL | Standard Deviation 3429.1 |
| OMT Only | NT Pro-BNP | -1069.9 pg/mL | Standard Deviation 6768.2 |
Secondary
Number of Subjects With HF Hospitalization
Rates of hospitalization or urgent clinic visit for worsening of heart failure and for any reason
Time frame: 2 days, 1 week, 1, 2, 3, and 6 months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| MV ASV+OMT | Number of Subjects With HF Hospitalization | 34 Participants |
| OMT Only | Number of Subjects With HF Hospitalization | 27 Participants |
Secondary
PHQ-9
The PHQ-9 is the nine item depression scale of the Patient Health Questionnaire. The PHQ-9 is a self-administered instrument for screening, diagnosing, monitoring and measuring the severity of depression. The PHQ-9 incorporates DSM-IV depression diagnostic criteria with other leading major depressive symptoms into a brief self-report tool. The tool rates the frequency of the symptoms which factors into the following scoring severity index: 0 - Not at all, 1 - Several Days, 2 - More than Half the Days, 3 - Nearly Every Day. Total score can range from 0 to 27. A higher score indicates increased severity.
Time frame: Change from Baseline to 6 months
Population: For endpoints that needed a change in measures from baseline to 6 months, if a subject missed one of the measurements, the subject was excluded from the analysis
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| MV ASV+OMT | PHQ-9 | -2.8 scores on a scale | Standard Deviation 6.7 |
| OMT Only | PHQ-9 | -4.6 scores on a scale | Standard Deviation 6.7 |
Secondary
PSQI
The Pittsburgh Sleep Quality Index is a 19-item subjective measurement of sleep. It is an effective instrument used to measure the quality and patterns of sleep in the older adult. It differentiates poor from good sleep by measuring seven areas: subjective sleep quality, sleep latency, sleep duration, habitual sleep efficiency, sleep disturbances, use of sleeping medication and daytime dysfunction over the last month. The subject self-rates each of these seven areas of sleep. The seven component scores are then added to yield a total score with a range of 0-21 points, 0 indicating no difficulty and 21 indicating severe difficulties in all areas.
Time frame: Change from Baseline to 6 months
Population: For endpoints that needed a change in measures from baseline to 6 months, if a subject missed one of the measurements, the subject was excluded from the analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| MV ASV+OMT | PSQI | -2.7 scores on a scale | Standard Deviation 5 |
| OMT Only | PSQI | -3.3 scores on a scale | Standard Deviation 4.9 |
Secondary
Six-minute Walk Distance
Change in functional parameters as measured by 6-minute walk test (6MWT)
Time frame: Change from Baseline to 6 months
Population: Reasons 6MWT was not performed:~In the MV ASV+OMT arm, 5 were discontinued prematurely, 3 participants could not walk, 4 participants were too critically ill, and 2 participants refused.~In the OMT only arm, 12 were discontinued prematurely, 1 participant could not walk, and 2 participants refused.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| MV ASV+OMT | Six-minute Walk Distance | 22.6 meters | Standard Deviation 131.3 |
| OMT Only | Six-minute Walk Distance | 61.2 meters | Standard Deviation 117.4 |
Secondary
Sleep Parameters
Sleep and sleep disordered breathing parameters (AHI, nocturnal hypoxemia)
Time frame: Change from Baseline to 6 months
Population: Not all subjects in the active arm successfully measured ODI. For endpoints that needed a change in measures from baseline to 6 months, if a subject missed one of the measurements, the subject was excluded from the analysis.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| MV ASV+OMT | Sleep Parameters | Change in AHI | -33.7 events per hour | Standard Deviation 16.9 |
| MV ASV+OMT | Sleep Parameters | Change in ODI | -28.3 events per hour | Standard Deviation 17.5 |
| OMT Only | Sleep Parameters | Change in AHI | -17.9 events per hour | Standard Deviation 22.3 |
| OMT Only | Sleep Parameters | Change in ODI | -16.3 events per hour | Standard Deviation 20.5 |
Secondary
Time Dead/Hospitalized
Total days dead or hospitalized at study end
Time frame: 6 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| MV ASV+OMT | Time Dead/Hospitalized | 23.9 number of days | Standard Deviation 39.3 |
| OMT Only | Time Dead/Hospitalized | 24.1 number of days | Standard Deviation 42.8 |
Secondary
Win Ratio
Patients in the new treatment and control groups are formed into matched pairs based on their risk profiles. For each matched pair, the new treatment patient is labeled a 'winner' or a 'loser' depending on who had a CV death first. If that is not known, they are labeled a 'winner' or 'loser' depending on who had a HF hospitalization first. Otherwise they are considered tied. The win ratio is the total number of winners divided by the total numbers of losers.
Time frame: 6 months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| MV ASV+OMT | Win Ratio | 0.97 Ratio |