Auto-PAP for Pulmonary Hypertension Treatment in Decompensated Heart Failure Patients With Obstructive Sleep Apnea: A Two Center Pilot Study
Phase: NA
Conditions: Sleep Apnea, Obstructive, Hypertension, Pulmonary, Heart Failure
Sponsor: Albert Einstein Healthcare Network

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STUDY PROTOCOL 
 
Auto-PAP for pulmonary hypertension treatment in decompensated heart failure 
patients with obstructive sleep apnea (ASAP-HF): A two center pilot study 
 
 
 
Study Number: ASAP-HF  
 
Version: Version 1.3 Final 
Date:  30 May 2017 
 
 
Principal Investigator: 
Sunil Sharma MD, FAASM 
Chair, Division of Pulmonary and Critical Care 
Director of Pulmonary Hypertension Program 
Einstein Medical Center, Philadelphia, PA 
 
 
 
 
 
 
This protocol has been written in accordance with current applicable guidelines (IDE for USA) as well as all 
other relevant additional references, medical and legal. 
 
 

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PROTOCOL REVISION HISTORY 
Version No. And Date 
Section 
Change 
Rationale 
Version 1.0 
25/08/2016 
10.4 
Removal of Contrast Echocardiogram 
Original Release/ 
Final Version 
Version 1.1 Final 
15/09/2016 
3 
6.2.5 
Addition of exclusion “patients 
weighing less than 66 pounds(30kg) 
Reflect device exclusion 
criteria 
Version 1.2 Final 
05/10/2016 
8.3 
Deleting section  ‘investigators are 
permitted to prescribe adjunctive 
medication per their medical 
discretion’ 
The attending physician 
will prescribe all  
medication related to the 
subject’s medical 
conditions 
Version: Version 1.3 
Final 
Date:  30 May 2017 
 
3 
6.2.3 
Up to 40 subjects overall will be 
randomized from in-patient clinical 
services to obtain endpoint data on 
20 evaluable subjects (10 evaluable 
patients on each site). This accounts 
for the expected dropout rate (50%). 
Increased number 
subjects enrolled, since a 
higher percentage are 
excluded after enrolled 
 
 

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Table of Contents 
1. 
Responsibilities and addresses .................................................................................................. 5 
2. 
ABBREVIATIONS AND DEFINITIONS ........................................................................................... 6 
3. 
PROTOCOL SUMMARY .............................................................................................................. 7 
4. 
INTRODUCTION ........................................................................................................................ 9 
4.1. 
Background Information ........................................................................................................... 9 
4.2. 
Intended Use ............................................................................................................................ 9 
5. 
STUDY OBJECTIVES ................................................................................................................... 9 
5.1. 
Primary Objective ..................................................................................................................... 9 
5.2. 
Primary Efficacy Endpoint Measurement ................................................................................ 10 
5.3. 
Secondary Objectives .............................................................................................................. 10 
5.4. 
Secondary Endpoint Measurements........................................................................................ 10 
6. 
DESIGN ................................................................................................................................... 10 
6.1. 
Enrollment .............................................................................................................................. 11 
6.2. 
Selection of subjects ............................................................................................................... 11 
6.2.1. 
Informed Consent ............................................................................................................. 11 
6.2.2. 
Study Population and Randomization ................................................................................ 11 
6.2.3. 
Number of Subjects ........................................................................................................... 11 
6.2.4. 
Subject Inclusion Criteria ................................................................................................... 11 
6.2.5. 
Subject Exclusion Criteria .................................................................................................. 12 
7. 
STUDY DEVICES ....................................................................................................................... 12 
7.1. 
AirSense 10 AutoSet ............................................................................................................... 12 
7.2. 
ApneaLink Air ......................................................................................................................... 13 
7.3. 
Device Accountability ............................................................................................................. 13 
7.4. 
Labeling .................................................................................................................................. 13 
7.5. 
Packaging ............................................................................................................................... 14 
7.6. 
Instruction for Use .................................................................................................................. 14 
8. 
THERAPY ................................................................................................................................. 14 
8.1. 
Treatment with AutoSet PAP (AirSense 10 AutoSet) ................................................................ 14 
8.2. 
Set up of AirSense 10 AutoSet ................................................................................................. 14 
8.3. 
Usual Medical Therapy............................................................................................................ 14 
9. 
STUDY SCHEDULE ................................................................................................................... 15 
9.1. 
Study Entry ............................................................................................................................. 15 
9.2. 
Study Flow .............................................................................................................................. 16 
9.3. 
Follow-Up, Procedures at the visits ......................................................................................... 17 
9.4. 
Screening Procedures ............................................................................................................. 17 
9.5. 
Detailed Visit Schedule ........................................................................................................... 18 
9.5.1. 
Baseline............................................................................................................................. 18 
9.5.2. 
Randomization .................................................................................................................. 18 
9.5.3. 
48hrs post-randomization ................................................................................................. 18 
9.5.4. 
End of Study ...................................................................................................................... 18 
9.6. 
Overview of procedures .......................................................................................................... 19 
9.7. 
Duration of the study .............................................................................................................. 19 
10. 
VISIT PROCEDURES ................................................................................................................. 19 
10.1. 
Cardiac Exam and Weight .................................................................................................. 19 
10.2. 
Polygraphy ........................................................................................................................ 20 
10.3. 
AirSense 10 AutoSet Device Set-up .................................................................................... 20 

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10.4. 
Echocardiography .............................................................................................................. 20 
10.5. 
Functional Capacity Testing (6MWT) ................................................................................. 20 
10.6. 
Biomarker testing and specimen storage ........................................................................... 21 
11. 
SAFETY .................................................................................................................................... 21 
11.1. 
Labeled Adverse Device Effects ......................................................................................... 21 
12. 
STATISTICAL ANALYSIS ............................................................................................................ 21 
12.1. 
Primary analysis ................................................................................................................ 22 
12.2. 
Secondary analyses ........................................................................................................... 22 
12.3. 
Justification of the Sample Size .......................................................................................... 22 
13. 
STOPPING AND DISCONTINUATION CRITERIA ......................................................................... 22 
13.1. 
Discontinuation Criteria Related to the Study .................................................................... 22 
13.2. 
Discontinuation Criteria related to the Subject .................................................................. 22 
14. 
DATA HANDLING AND RECORDKEEPING ................................................................................. 23 
14.1. 
Data Collection .................................................................................................................. 23 
14.2. 
Study Documentation ........................................................................................................ 23 
14.3. 
Query Generation and Resolution ..................................................................................... 23 
14.4. 
Data Storage ..................................................................................................................... 23 
14.5. 
Study Files and Record Retention ...................................................................................... 23 
14.6. 
Regulatory Documentation ................................................................................................ 24 
15. 
ETHICAL CONSIDERATIONS ..................................................................................................... 24 
15.1. 
Institutional Review Board (IRB)/Ethics Committee (EC) .................................................... 24 
15.2. 
Protocol Deviations ........................................................................................................... 24 
15.3. 
Risk Analysis and Confidentiality ........................................................................................ 25 
15.3.1. 
Risk Determination of the Study ........................................................................................ 25 
15.3.2. 
Subject Data Confidentiality .............................................................................................. 25 
16. 
QUALITY CONTROL AND QUALITY ASSURANCE........................................................................ 26 
16.1. 
Site Selection ..................................................................................................................... 26 
16.2. 
Polygraphy Data ................................................................................................................ 26 
16.3. 
Six-Minute Walk Test ......................................................................................................... 26 
16.4. 
Echocardiograhpy .............................................................................................................. 26 
16.5. 
Training ............................................................................................................................. 26 
16.6. 
Site Monitoring ................................................................................................................. 26 
16.7. 
Audits and Inspections ...................................................................................................... 26 
17. 
RESPONSIBILITIES.................................................................................................................... 27 
17.1. 
Clinical Investigator Responsibilities .................................................................................. 27 
18. 
STUDY REPORTS AND PUBLICATIONS ...................................................................................... 27 
19. 
REFERENCES ........................................................................................................................... 28 
 
 
 

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1. Responsibilities and addresses 
Principal Investigator (US): Sunil Sharma MD, FAASM 
Chair, Division of Pulmonary and Critical Care 
Director of Pulmonary Hypertension Program 
Einstein Medical Center, Philadelphia, PA 
 
Principal Investigator (Germany): Olaf Oldenburg, MD 
Heart and Diabetes Center NRW 
Ruhr University of Bochum 
Georgstraße 11 
D-32545 Bad Oeynhausen 
Phone:  
Email: OOldenburg@hdz-nrw.de 
 
 
 

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2. ABBREVIATIONS AND DEFINITIONS  
6MWD 
Six-minute walk distance 
6MWT 
Six-minute walk test 
AE 
Adverse Event 
AHI 
Apnea-Hypopnea Index 
APAP 
Auto-adjusting positive airway pressure 
BNP 
B-type natriuretic peptide 
CHF 
Congestive heart failure 
COPD 
Chronic obstructive pulmonary disease 
CPAP 
Continuous Positive Airway Pressure 
EC 
Ethics Committee 
ECG 
Electrocardiogram 
ECHO 
Echocardiography 
eCRF 
Electronic Case Report Form 
EDC 
Electronic Data Capture 
E/e' 
Ratio of early transmitral flow velocity to early diastolic mitral annular velocity 
e/hr 
Events per hour 
EF 
Ejection Fraction 
EPAP 
Expiratory Positive Airway Pressure 
FDA 
Food and Drug Administration 
HF 
Heart Failure 
HFpEF 
Heart failure with preserved ejection fraction 
HFrEF 
Heart failure with reduced ejection fraction 
IDE 
Investigational Device Exemption 
IRB 
Institutional Review Board 
LV 
Left Ventricular 
LVAD 
Left ventricular assist device 
LVEDP 
Left ventricular end diastolic pressure 
LVEF 
Left ventricular ejection fraction 
NT pro-BNP 
N-terminal prohormone of b-type natriuretic protein 
NYHA 
New York Heart Association 
OSA 
Obstructive Sleep Apnea 
PA 
Pulmonary arterial 
PAP 
Positive Airway Pressure 
PV 
Pulmonary ventricular 
RA 
Right arterial 
SAE 
Serious Adverse Event 
SDB 
Sleep-Disordered Breathing 
SOP 
Standard Operation Procedures 
UADE 
Unanticipated adverse device effect 

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3. PROTOCOL SUMMARY 
Objectives 
The objective of the study is to evaluate the effect of continuous positive airway 
pressure (PAP) therapy on pulmonary arterial (PA) pressures in acute decompensated 
heart failure (HF) patients with obstructive sleep apnea (OSA). The study will also 
assess changes in functional parameters, biomarkers, and echocardiographic 
parameters. 
Study Design 
This study is a randomized, unblinded, two-center trial with parallel group design, with 
subjects randomized to either control (no PAP therapy) or active treatment (PAP 
therapy) in a 1:1 ratio.  
Number of 
Subjects 
Up to 40 subjects overall will be randomized from in-patient clinical services to obtain 
endpoint data on 20 evaluable subjects (10 evaluable patients on each site). This 
accounts for the expected dropout rate (50%). 
Selection 
criteria 
 
Inclusion criteria for the study are: 
1. Age 18 years or more 
2. Decompensated CHF with systolic PA pressures of ≥50 mmHg (including RA 
pressure) 
3. Prior clinical diagnosis of heart failure (HFrEF or HFpEF) 
4. Moderate to Severe predominately obstructive SDB documented by polygraphy 
with AHI ≥20e/h and 5% of the time spent <90% O2 Sat (minimum 2hr 
recording time) 
5. Patient is able to fully understand study information and sign informed consent 
Exclusion criteria for the study are: 
1. Chronic renal insufficiency (HD or serum creatinine > 2) 
2. Hemodynamically significant valvular disease 
3. Severe arthritis or inability to complete 6MWT 
4. LVAD/ heart transplant or hemodynamically unstable 
5. Patient taking any Pulmonary vasodilators, including home oxygen.  
6. Known diagnosis of OSA and on active therapy 
7. 80% of the respiratory events being central/Cheyne-Stokes breathing (SERVE-HF 
criteria) 
8. Recent cardiac surgery (within 30 days of admission) 
9. Recent stroke (within 30 days of admission or with persistent neurological 
deficits) 
10. Severe COPD defined as FEV1 < 50%  
11. Chronic renal failure on hemodialysis 

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12. Participation in a randomized controlled pharmaceutical or treatment-related 
cardiac or pulmonary clinical study within 1 month prior to randomization. 
13. Patient weighing less than 66 pounds(30kg) 
Primary 
Endpoints 
Reduction in PA systolic pressure as measured by Echocardiogram over 48 hrs.  
Secondary 
Endpoints 
1. Change in functional parameters as measured by 6-minute walk test (6MWT) 
2. Change in neurohumoral activation as measured by N-terminal pro b-type 
natriuretic peptide (NT pro-BNP) 
3. Change in blood oxygenation as measured by arterial blood gas analysis 
4. Heart failure symptoms as assessed by the New York Heart Association scale 
(NYHA) classification  
5. Change in fluid retention as measured by weight 
6. Echocardiographic parameters, including E/e’ as assumption of LVEDP and PV 
acceleration time 
7. Length of hospital stay 
Scheduled 
follow up 
For evaluation of the primary endpoint, subjects will be followed for a period of 48 
hours while in hospital.  
Polygraphy, including pulse oximetry (ApneaLink Air) will be performed at screening. 
The following tests will be performed at baseline and at 48hrs: 
 Cardiac exam (including NYHA class and weight measurement) 
 Echocardiography 
 Functional capacity testing (6MWD) 
 Blood collection 
 Blood gas analysis 
 
 
 

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4. INTRODUCTION 
4.1. Background Information 
Pulmonary hypertension (PH) in the setting of congestive heart failure (CHF) is common, a marker 
of poor prognosis, and associated with accelerated mortality1,2,3. Currently available treatments 
targeted at secondary PH in CHF have not yielded positive results, which still leaves these patients 
with no productive therapy option today. Obstructive sleep apnea (OSA) is highly prevalent and 
still largely under-diagnosed in CHF patients4. OSA is believed to have significant hemodynamic 
impact, which may play a role in development of pulmonary hypertension. Prior studies have 
shown that pulmonary pressures increase during sleep even in normal subjects5. In patients with 
OSA the PA pressures increase over different stages with a further spike in REM stage with 
opposite effect on alveolar ventilation6. The pathophysiology of pulmonary hypertension due to 
OSA is believed to be due to generation of significant intra-pleural negative pressures due to 
glottic closure and intermittent hypoxia causing pulmonary vasoconstriction6,7,8,9,10,11 leading to 
increased pulmonary pressures6. Treatment with tracheostomy and continuous positive airway 
pressure therapy has shown to improve pulmonary artery pressures6,12,13. Our preliminary data 
from a retrospective review of heart failure service revealed significant reduction in PA pressures 
in patients compliant with positive airway pressure therapy13. Therefore, it is reasonable to 
hypothesize that therapy with Automatic positive airway pressure (APAP) with fixed lower EPAP 
pressures may have a salutary effect on the PA pressures in the acute setting . 
We hypothesize that acute inpatient intervention with auto-adjusting positive airway pressure 
therapy (APAP) in patients with decompensated CHF and OSA may significantly reduce PA 
pressures, and also reduce length of stay (LOS) and NT-proBNP levels leading to improved patient 
outcome. With this approach APAP may offer a novel therapy option for these comorbid patients, 
desperately seeking for improvements in symptoms. 
4.2. Intended Use 
The AirSense™ 10 AutoSet™ device is cleared for use by the US FDA with the following indication: 
The AirSense 10 AutoSet self-adjusting device is indicated for the treatment of obstructive sleep 
apnea (OSA) in patients weighing more than 66 lb (30 kg). It is intended for home and hospital use. 
The humidifier is intended for single patient use in the home environment and re-use in a 
hospital/institutional environment. 
5. STUDY OBJECTIVES 
5.1. Primary Objective 
The primary objective of this pilot study is to evaluate the effect of continuous positive airway 
pressure (PAP) therapy on pulmonary arterial (PA) pressures in acute decompensated heart failure 

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(HF) patients with severe obstructive sleep apnea (OSA). The study will also assess changes in 
functional parameters, biomarkers, and echocardiographic parameters. 
5.2. Primary Efficacy Endpoint Measurement 
The primary endpoint is reduction in PA pressures after 48 hrs, with a minimum 8hrs APAP 
therapy. 
5.3. Secondary Objectives 
1. To compare changes in functional parameters (6MWD) from baseline to 48hrs  
2. To compare changes in NT pro-BNP from baseline to 48hrs 
3. To compare changes in blood oxygenation from baseline to 48hrs 
4. To compare changes in heart failure symptoms from baseline to 48hrs 
5. To compare changes in fluid retention from baseline to 48hrs  
6. To compare changes in echocardiographic parameters, including E/e’ as assumption of 
LVEDP and PV acceleration time from baseline to 48hrs  
7. To compare hospital length of stay between groups  
5.4. Secondary Endpoint Measurements 
1. Change in functional parameters as measured by 6-minute walk test (6MWT) 
2. Change in neurohumoral activation as measured by N-terminal pro b-type natriuretic 
peptide (NT pro-BNP) 
3. Change in blood oxygenation as measured by blood gas analysis 
4. Heart failure symptoms as assessed by the New York Heart Association scale (NYHA) 
classification  
5. Change in fluid retention as measured by weight 
6. Echocardiographic parameters, including E/e’ as assumption of LVEDP and PV acceleration 
time 
7. Difference in length of stay between study groups 
6. DESIGN 
The ASAP-HF study is a prospective, randomized, controlled, two-center, study with a parallel group 
design, with subjects randomized to either control (no APAP) or active treatment (APAP) in a 1:1 ratio.  
This study will be conducted in one center in the US and one center in Germany.  

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6.1. Enrollment 
Subjects will be recruited from in-patient clinical services. If a subject is willing to participate in the 
ASAP-HF study, a written informed consent for the study must be obtained prior to any study 
related procedure. Before randomization, all eligibility criteria must be confirmed.  
6.2. Selection of subjects 
6.2.1. 
Informed Consent 
The consent form is written in accordance with applicable data privacy acts and FDA 
Regulations and approved by the responsible Institutional Review board (IRB)/Ethics 
Committee (EC).  
The investigator or responsible staff will explain the nature, purpose and risks associated 
with the study. The patient will be given sufficient time to consider the study’s 
implications before deciding whether to participate. Information materials created by 
the investigators must be approved by the responsible IRB/EC prior to use.  
A signed, IRB/EC-approved consent form must be obtained from the patient prior to the 
performance of any protocol-related testing or treatment procedures. The consent 
process must be performed by a designated clinical study team member authorized by 
the IRB/EC to consent patients and listed on the Delegation of Authority Log as having 
privileges to consent patients. A signed copy of the consent form must be maintained in 
the study files and a copy provided to the patient. The patient’s permanent medical 
records should indicate study participation.  
6.2.2. 
Study Population and Randomization 
Enrolled subjects who fulfill the inclusion criteria and none of the exclusion criteria for 
the ASAP-HF study and who sign the consent form(s) are considered as potential 
candidates for randomization to either control or active treatment arm in a ratio of 1:1. 
Subjects will be randomized to one of the treatment options, Group A (active): standard 
medical therapy plus treatment with continuous APAP for 48hrs, or Group B (control): 
standard medical therapy only. 
6.2.3. 
Number of Subjects 
Up to 40 subjects will be randomized in order to achieve 20 evaluable subjects (10 per 
arm and 10 per site).   
6.2.4. 
 Subject Inclusion Criteria 
1. Age 18 years or more 
2. Decompensated CHF with systolic PA pressures of ≥50 mmHg (including RA pressure) 

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3. Prior clinical diagnosis of heart failure (HFrEF or HFpEF) 
4. Moderate to Severe predominately obstructive SDB documented by polygraphy with AHI 
≥20e/h and 5% of the time spent <90% O2 Sat (minimum 2hr recording time) 
5. Patient is able to fully understand study information and sign informed  
6.2.5. 
Subject Exclusion Criteria  
1. Chronic renal insufficiency (HD or serum creatinine > 2) 
2. Hemodynamically significant valvular disease 
3. Severe arthritis or inability to complete 6MWT 
4. LVAD/ heart transplant or hemodynamically unstable 
5. Patient taking any Pulmonary vasodilators, including home oxygen.  
6. Known diagnosis of OSA and on active therapy 
7. 80% of the respiratory events being central/Cheyne-Stokes breathing (SERVE-HF criteria) 
8. Recent cardiac surgery (within 30 days of admission) 
9. Recent stroke (within 30 days of admission or with persistent neurological deficits) 
10. Severe COPD defined as FEV1 < 50%  
11. Chronic renal failure on hemodialysis 
12. Participation in a randomized controlled pharmaceutical or treatment-related cardiac or 
pulmonary clinical study within 1 month prior to randomization. 
13. Patient weighing less than 66 pounds(30kg) 
7. STUDY DEVICES 
7.1. AirSense 10 AutoSet 
The AirSense 10 AutoSet (“AutoSet”) is a market-released device that has been FDA-cleared 
(K140124) in the US and CE-marked in Germany (EC149) to provide non-invasive ventilatory 
support to treat patients weighing more than 66 lbs (30 kg). The device is intended for home and 
hospital use. 
The treatment pressure required by the patient may vary due to changes in sleep state, body 
position and airway resistance. In AutoSet mode, the device provides only that amount of pressure 
required to maintain upper airway patency. 
The device analyzes the state of the patient’s upper airway on a breath-by-breath basis and 
delivers pressure within the allowed range according to the degree of obstruction. The AutoSet 

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algorithm adjusts treatment pressure as a function of three parameters: inspiratory flow 
limitation, snore, and apnea. 
Ancillary equipment includes the humidifier, air delivery hose, mask, and headgear. The AirSense 
10 AutoSet provides a minimum and maximum pressure within the range of 4-20 cm H2O. 
See AirSense 10 AutoSet Clinician's Manual for details. 
7.2. ApneaLink Air 
The ApneaLink Air is a market-released polygraphy device that has been FDA-cleared (K143272) for 
use by Health Care Professionals, where it may aid in the diagnosis of sleep disordered breathing 
for adult patients. ApneaLink Air records the following data: patient respiratory nasal airflow, 
snoring, blood oxygen saturation, pulse, and respiratory effort during sleep. ApneaLink Air uses 
these recordings to produce a report that may aid in the diagnosis of sleep disordered breathing or 
for further clinical investigation. The ApneaLink Air may be used with an optional dual-lumen 
cannula in cases where the patient cannot be taken off oxygen for the duration of the test. 
The ApneaLink Air recorder is a 3-channel battery-powered respiratory pressure sensor and 
oximetry system. The ApneaLink Air recorder and the respiratory effort sensor must be fastened 
with the re-usable belt on the patient's chest. All relevant respiratory information during sleep will 
be collected via nasal cannula, pulse oximetry adapter and respiratory effort sensor. The 
disposable plastic nasal cannula is connected to the ApneaLink Air recorder and fixed at the 
patient's nose. The oximetry sensor is connected to the patient's finger. The respiratory effort 
sensor is connected to the ApneaLink recorder and held in place by the belt. With the ApneaLink 
Air Software installed on a personal computer, the physician can generate a report with the 
recorded and analyzed data. The default settings for the ApneaLink Air includes a flow reduction of 
30% combined with a desaturation of 4% to automatically score a hypopnea and a respiratory 
effort sensor to differentiate between central, obstructive and mixed apneas.  
See ApneaLink Air Clinician's Manual in study Manual of Procedures for details. 
7.3. Device Accountability 
An accurate and current accounting of the dispensing of ResMed devices (AirSense 10 AutoSet, 
ApneaLink Air) will be maintained on an on-going basis by a qualified member of the study site 
using a “Device Disposition Log”. Devices will be made available to the investigator by ResMed. If a 
replacement device is dispensed, it will be documented per device accountability procedure.  
7.4. Labeling 
The label contains the information as required by relevant regulatory requirements: 
a) Manufacturer name and address 
b) Serial number to identify the individual device 

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c) Instruction For Use 
7.5. Packaging 
The AirSense 10 AutoSet and ApneaLink Air study devices are FDA 510(k) cleared in the US and are 
CE marked according to the European Declaration of Conformity. The devices will be used with the 
standard packaging.  
7.6. Instruction for Use 
The devices will be used as specified in the relevant Instructions for Use. 
8. THERAPY 
8.1. Treatment with AutoSet PAP (AirSense 10 AutoSet) 
The AirSense 10 AutoSet device will be used in the hospital. Although the AutoSet device has two 
therapy modes, CPAP and AutoSet, only the AutoSet mode will be used for this study. The device 
will be used continuously for 48hrs while the subject is in hospital except when eating, using the 
bathroom, or going for a test. Subjects who are not able to use the device for at least 5hrs in a 
24hr period or 8hrs over the 48hr period will be excluded from analysis.  
8.2. Set up of AirSense 10 AutoSet 
For initiation of therapy, the AutoSet device will be set to a minimum expiratory PAP (EPAP) of 8 
cmH20, a maximum EPAP of 15 cmH2O. EPAP may be lowered to up to 6 cm if patient unable to 
tolerate higher EPAP.All subjects will be provided humidifiers and ClimateLine tubing to address 
any instance of upper airway dryness or other forms of discomfort with the airflow of the device 
during the initiation or during therapy with the device. For the initiation of therapy, a ResMed full 
face mask is recommended, but if this mask is unsuitable for the subject another type of mask 
such as a nasal mask will be tried. Subjects who are unable to tolerate EPAP of 8 cm of H2O 
pressure will be given an acclimation trial over 2 hours at lower pressures. If despite the 
acclimation trial the subject is unable to tolerate the pressure, they will be discharged from the 
study.  
8.3. Usual Medical Therapy 
All subjects should be treated with usual therapy for heart failure in accordance to the applicable 
guidelines, particularly with reference to medication. Other guideline-recommended therapies 
should be encouraged. All medications will be documented. 

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9. STUDY SCHEDULE 
9.1. Study Entry 
A patient meets eligibility criteria of the study if all of the inclusion criteria and none of the 
exclusion criteria are met.  

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9.2. Study Flow 
 
Identify potential subject at least 24 hrs since presentation 
(Dx of HF, dyspnea, S&Sx of ADHF, PA pressure >50mmHg) 
Other Exclusion Criteria present? 
Enter subject in database 
Perform ApneaLink Air test 
AHI≥20 e/hr on ApneaLink Air AND 
able to perform 6MWT? 
Subject participation confirmed  
Complete all baseline evaluations, including 
blood collection, ECHO, and 6MWT  
Subject randomized 1:1 
Group A: Usual Medical 
Therapy plus AutoSet 
Group B: Usual 
Medical Therapy 
AutoSet setup; continuous AutoSet 
use for 48hrs, including oximetry  
End of Study 
Document length of hospital stay 
No further action 
– ineligible for 
study 
Subject not 
randomized  
Yes 
Yes 
Yes 
No 
No 
No 
No 
Yes
Yes
Perform post-48hr tests, including 6MWT, 
ECHO, NT-proBNP 
Obtain Informed Consent 
Yes 

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9.3. Follow-Up, Procedures at the visits 
The clinical study plan of the ASAP-HF study includes monitoring the subject while in hospital, and 
evaluations after 48hrs relative to the time of randomization.  
At the end of the study, for subjects in both arms of the study, there will be a discussion regarding 
management of the subject’s sleep-disordered breathing. 
See Section 10 for description of specific study procedures. 
9.4. Screening Procedures 
Patients who have been admitted to the hospital with symptoms of acute decompensated heart 
failure will first be evaluated for eligibility for the study based on chart review. Permission to 
review records will be requested to conduct preliminary chart review and interview. Review the 
patient's records to ensure the following: 
1. The patient is hospitalized and has signs and symptoms of acute decompensated HF as 
determined by dyspnea and elevated BNP as listed in inclusion criteria. 
2. The patient is able to perform the 6MWT (i.e., is not wheelchair-bound). 
3. The patient has PA pressures of ≥50mmHg 
If the patient appears to be eligible based on the initial cardiology-related entry criteria, they may 
be approached about study participation and consent obtained.  
NOTE: All subjects who sign a consent form must be entered in the data management system, 
whether or not they are randomized into the study. 
1. Document demographics and eligibility criteria data  
2. Arrange for AHI measurement using the ApneaLink Air overnight (see Section 10.2). Subject is 
not eligible for study entry if AHI<20 e/hr from ApneaLink Air. 
3. If ApneaLink Air results show AHI≥20 e/hr with at least 2hr recording time and 5% of time 
<90% O2Sat and other entry criteria are met, then subject is considered enrolled in the study.   
 
 

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9.5. Detailed Visit Schedule 
The following visit schedule applies to subjects who met all eligibility criteria, and are enrolled in 
the ASAP-HF study. Document the following in the subject’s medical record (source 
documentation). 
9.5.1. Baseline  
Treatment 
Group 
 
A 
B 
Perform cardiac exam (including NYHA) and record vitals (including weight) 
X 
X 
Document all medications 
 
 
Perform echocardiography 
X 
X 
Conduct exercise capacity testing (6MWT)  
X 
X 
Draw blood for NT-proBNP testing. 
X 
X 
 
9.5.2. Randomization 
Treatment 
Group 
 
A 
B 
When all baseline assessment have been completed, the subject will be randomized to 
Group A (Usual Medical Treatment + continuous AutoSet therapy) or  
Group B (Usual Medical Treatment alone).  
Subjects randomized to Group A should begin using the AutoSet device immediately. 
Mask fitting and AutoSet device set up 
X 
 
Assess for issues with mask or AutoSet device  
X 
 
Begin continuous AutoSet therapy while awake and asleep 
X 
 
 
 
9.5.3. 48hrs post-randomization 
Treatment 
Group 
 
A 
B 
Stop AutoSet therapy; download device data 
X 
 
Perform cardiac exam (including NYHA) and record vitals (including weight) 
X 
X 
Document all medications 
X 
X 
Perform echocardiography 
X 
X 
Conduct exercise capacity testing (6MWT)  
X 
X 
Draw blood for NT-proBNP testing 
X 
X 
Assess for issues with mask or AutoSet device  
X 
 
 
9.5.4. End of Study  
Treatment 
Group 
 
A 
B 
Discuss options for management of SDB 
X 
X 
Assess for issues with mask or AutoSet device  
X 
 
Assess for issues with sleep hygiene 
X 
X 

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Document length of hospital stay 
X 
X 
 
9.6. Overview of procedures 
 
Screening 
Baseline 
48hrs 
End of Study 
Visit Location:  
In Hospital 
In Hospital 
In Hospital 
In Hospital 
 Review of HF history, signs & symptoms 
X 
 
 
 
ApneaLink Air test 
X 
 
 
 
Cardiovascular examination  
(includes ECG and NYHA) 
 
X 
X 
 
Echocardiography 
 
X 
X 
 
Exercise capacity testing (6MWT) 
 
X 
X 
 
Initiation of continuous AutoSet Therapy1  
 
X 
 
 
AutoSet Device download1  
 
 
X 
 
AE monitoring 
 
X 
X 
X 
Assess mask or AutoSet issues1  
 
X 
X 
X 
Labs (NT pro-BNP) 
 
X 
X 
 
Post study SDB management plan 
 
 
 
X 
1 Group A only. 
 
9.7. Duration of the study 
An individual randomized subject’s participation is expected to be 48hrs. The overall study 
duration is calculated to be approximately 6 months. 
10. VISIT PROCEDURES 
10.1. Cardiac Exam and Weight 
The cardiovascular exam should include heart sounds, rhythm, pulses, breath sounds, as well as 
standardized blood pressure, heart rate, respiration rate, routine local lab tests, vitals (including 
weight) and ECG.  
The New York Heart Association (NYHA) Functional Classification14 provides a simple way of 
classifying the extent of heart failure. It places patients in one of four categories based on how 
much they are limited during physical activity; the limitations/symptoms are in regard to normal 
breathing and varying degrees in shortness of breath and or angina pain: 
NYHA Class 
Symptoms 
I 
Cardiac disease, but no symptoms and no limitation in ordinary physical 
activity, e.g. shortness of breath when walking, climbing stairs etc. 
II 
Mild symptoms (mild shortness of breath and/or angina) and slight 
limitation during ordinary activity. 

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III 
Marked limitation in activity due to symptoms, even during less-than-
ordinary activity, e.g. walking short distances (20–100 m). 
Comfortable only at rest. 
IV 
Severe limitations. Experiences symptoms even while at rest. Mostly 
bedbound patients. 
NYHA Class determination should be performed by an independent assessor who is blinded to the 
subject's treatment group once the subject has been randomized. 
10.2. Polygraphy 
Every subject in the study will undergo polygraphy (including pulse oximetry) using ApneaLink Air 
at screening while in hospital. Data acquisition and analysis is described in the ApneaLink Systems 
Clinical Guide and data collection and the settings required for automatic scoring will be described 
in the Manual of Procedures. Completion of the test is defined as the time the report is generated. 
10.3. AirSense 10 AutoSet Device Set-up 
All subjects meeting eligibility criteria and randomized into Group A will be fitted with a mask and 
set up on the AirSense 10 AutoSet device. Subjects who are unable to tolerate EPAP of 8 cm H2O 
pressure will be given an acclimation trial over 2 hours at lower pressures. If despite the 
acclimation trial the subject is unable to tolerate the pressure, they will be discharged from the 
study. 
10.4. Echocardiography 
Echocardiogram image acquisition protocols and procedures are provided in the Manual of 
Procedures. Resting transthoracic 2-D and Doppler echocardiograms will be performed in subjects 
at admission and at 48 hours post PAP therapy at the enrolling site for a comprehensive evaluation 
of systolic function, diastolic function and Doppler parameters. The primary echocardiographic 
endpoints are the change over time between treatment and control groups for the following 
parameters: Pulmonary artery systolic pressure (PASP), Right atrial pressures (RAP), Tricuspid 
regurgitation (TR) jet, left ventricular ejection fraction (LVEF), and left ventricular systolic volume 
index (LVSVI) for subjects with reduced EF (HFrEF, LVEF <45%), and the ratio of transmitral Doppler 
early filling velocity to tissue Doppler early diastolic mitral annular velocity determinant of mean 
left atrial pressure (E/e‘) in subjects with preserved EF (HFpEF, LVEF≥45%). Echocardiograms 
should be performed at the time of discontinuation of PAP therapy. 
10.5. Functional Capacity Testing (6MWT) 
The 6-Minute Walk Test (6MWT) serves as an objective evaluation of the response to medical 
intervention. The distance walked in 6 minutes (6MWD) on a hard, flat surface is measured. The 
6MWT will be performed according to standard operating procedures specified for this protocol 
(see Manual of Procedures). All subjects will be assessed for clinical stability immediately prior to 

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exercise and a physician will be in attendance during the test. Exercise will be performed on a level 
indoor surface following American Thoracic Society (ATS) guidelines in a way that minimizes 
variability. If there are any signs of medical instability, the attending physician will end the test 
before 6 minutes. 
10.6. Biomarker testing and specimen storage 
Blood will be collected and processed to obtain samples for NTpro-BNP. All samples will be sent to 
the site’s local clinical laboratory for testing.  
11. SAFETY 
The investigator is responsible for monitoring the safety of subjects enrolled into the study at the 
study site. The investigator or qualified designee will enter the required initial and follow-up 
information regarding events on the appropriate eCRF within the EDC system. Investigators are 
responsible for following all serious adverse events (SAEs) until resolution, stabilization, or the 
event is otherwise explained, and to report serious adverse events as well as serious injury or 
death that were related to (caused by or contributed to) the AirSense 10 AutoSet study device in 
accordance with their local IRB/EC requirements. Investigators should follow usual clinical practice 
at their institutions for reporting serious events to the regulatory authorities.  
11.1. Labeled Adverse Device Effects 
Expected adverse device events are determined to be mild and are related to the interface (mask) 
between the AutoSet device and the subject. In this study any skin or eye irritation that is transient 
(ie, resolves within 24 hours following device use and requires no medical intervention), will not be 
classified as an adverse device effect. 
Mask  
 
Mild skin irritation around the nose and forehead from the mask 
 
Mild facial abrasions from ill-fitting mask interface  
 
Eye irritation, caused by leakage of air from the sides of the mask  
Flow Generator 
 
Drying of the nose, mouth, or throat 
 
Nosebleed 
 
Bloating 
 
Ear or sinus discomfort 
 
Eye irritation 
 
Skin rashes 
12. STATISTICAL ANALYSIS 
Descriptive summaries including medians, 25th and 75th percentiles will be presented for continuous 
variables; the number and frequency of subjects in each category will be presented for nominal 

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variables. Statistical tests with a two-sided p-value <0.05 will be considered statistically significant, 
unless otherwise specified. Analyses will be performed using validated software. Appropriate statistical 
models will be used to examine the effect of continuous APAP treatment on both the primary and 
secondary outcomes in the study. For continuous response (endpoint) variables, conventional general 
linear models will be used. For endpoints where the response is dichotomous (binary), the logistic 
regression model will be used. For time-to-event endpoints, the Cox regression model will be used. 
Subject flow will be described using a CONSORT style diagram15. The primary analysis will be conducted 
on an intention-to-treat (ITT) basis. The ITT population includes all participants who are randomized. 
12.1. Primary analysis 
To be determined   
12.2. Secondary analyses 
Continuous secondary endpoints will be analyzed analogously, possibly log-transformed if 
appropriate. Categorical endpoints will be compared using a Fisher’s exact test.  
12.3. Justification of the Sample Size 
Pilot study 
13. STOPPING AND DISCONTINUATION CRITERIA 
It is estimated that up to 22 subjects will be recruited to obtain the 20 evaluable subjects required for 
the primary endpoint. 
13.1. Discontinuation Criteria Related to the Study 
Discontinuation of the study may be decided due to safety events as determined by the Principal 
Investigators.  
Each site investigator will oversee the patient safety at his/her site, including the review of all 
Serious Adverse Events (SAEs) and unanticipated adverse device effects (UADEs), ensuring that 
appropriate study data are communicated to the subject‘s physicians and the IRB/EC, and that 
appropriate referrals or interventions are initiated. Major unanticipated adverse events and 
unanticipated product problems will be reported to the IRB/EC.  
13.2. Discontinuation Criteria related to the Subject 
The subjects will be advised in the consent form that they have the right to withdraw from the 
study at any time without prejudice. In the event that a subject drops out of the study, the Study 
Termination CRF should be completed. In the Study Termination CRF the investigator should 
record the reason for the subject‘s termination. Once randomized, the subject stays within his/her 
group, and will be followed to the end of the study. Those subjects in whom protocol deviation or 

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violation is noticed will remain in the intention-to-treat group and will be followed according to 
protocol.  
14. DATA HANDLING AND RECORDKEEPING 
14.1. Data Collection 
During the study, the investigator, sub-investigator(s), or study coordinator participating in the 
study will record progress notes to document all data required by the protocol. 
Any changes to information in the study progress notes, or other source documents, must be 
initialed and dated on the date the change is made by a clinician authorized to make the change. 
14.2. Study Documentation 
Throughout the conduct of the study, all required data will be entered into the eCRF for each 
subject. The investigator should ensure the accuracy, completeness, and timeliness of the data 
reported in the eCRFs and in all required reports. Data entered into the eCRF must be consistent 
with source documents. Any change or correction to an eCRF will be captured in the EDC system 
audit trail.  
The site PI or designee and the clinical monitor will review completed eCRFs for accuracy, 
discrepancies, and missing information.  
14.3. Query Generation and Resolution 
Queries will be generated based upon anomalous or missing data and will be tracked via the EDC 
System. 
Once all queries are resolved, the database will be verified by ensuring all electronic files were 
completely and correctly loaded. In addition, as part of the routine site monitoring, source 
documentation should be reviewed against data entered into the EDC System. 
14.4. Data Storage 
Access to data maintained in the EDC System is strictly limited to authorized personnel. 
14.5. Study Files and Record Retention 
The investigator must maintain adequate and accurate records as specified in Essential Documents 
for the Conduct of a Clinical Trial (E6, Section 8 of the ICH Guideline for GCP) to enable the conduct 
of the study to be fully documented and the study data to subsequently be verified. These 
documents should be classified into two separate categories: (1) investigator’s study file and (2) 
subject clinical source documents. 

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Essential documents must be retained until at least 2 years after the investigations have been 
discontinued OR 2 years after the last approval of a marketing application.  
14.6. Regulatory Documentation 
Documents that must be maintained in the study files: 
 
Signed, dated current (within 2 years) curriculum vitae of Investigator and Sub-Investigator(s) 
 
Assurance that the IRB/EC complies with requirements set forth in Title 21 Part 56 of the Code 
of Federal Regulations. The required documentation consists of name and address of the 
IRB/EC, a current list of members including title, gender, occupation and any institutional 
affiliation of each member. A general assurance number from the Department of Health and 
Human Services may be substituted for this list. 
 
Written notification (copy) to the Investigator from the IRB/EC approving the protocol 
 
IRB/EC approved informed consent (copy) and any other adjunctive materials to be used in the 
study as required. 
15. ETHICAL CONSIDERATIONS 
15.1. Institutional Review Board (IRB)/Ethics Committee (EC) 
The investigator must have written and dated approval from the IRB/EC for the protocol, consent 
form, subject recruitment materials/process (advertisements), and any other written information 
to be provided to subjects. The investigator should also provide the IRB/EC with a copy of the 
product labeling information and any updates. The investigator will provide the IRB/EC with 
reports, updates, and other information (e.g., safety updates and protocol amendments) as 
required by regulations. 
15.2. Protocol Deviations 
An investigator is required to conduct this study in accordance with this Investigational Plan, 
applicable laws and FDA regulations, and any conditions of approval imposed by the reviewing 
IRB/EC and FDA. According to FDA regulation 21 CFR § 812.150(a)(4), an investigator shall notify 
the reviewing IRB/EC of any deviation from the investigational plan to protect the life or physical 
well-being of a subject in an emergency. Such notice shall be given as soon as possible, but no later 
than five working days after the emergency occurred.  
A list of subjects with protocol deviations will be compiled based on entry criteria deviations as 
well as deviations from study conduct and assessments. Prior to data base lock, an evaluation of 
subjects with significant protocol deviations will be performed to assess the appropriateness of 
their inclusion in the analysis. 

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15.3. Risk Analysis and Confidentiality 
15.3.1. 
Risk Determination of the Study 
The AirSense 10 AutoSet device has been cleared (K140124) by FDA to provide self-adjusting 
treatment of obstructive sleep apnea (OSA) in patients weighing more than 66 lbs (30 kg). The 
device is intended for home and hospital use. The purpose of this study is to evaluate the effect of 
an adjunctive therapy on the hemodynamics of adult patients with acute decompensated heart 
failure and severe sleep apnea. Continuously treating the patient with the device over a short 
period of time is hypothesized to affect the pulmonary arterial pressure in these patients. 
Clinical personnel will observe the subject on the fitting and use of the AutoSet device. They will 
monitor the subject’s clinical parameters, which include hemodynamics and will intervene, if 
required. 
This study is considered to be of minimal risk to the patients assigned to the AutoSet arm of the 
study. PAP therapy is the most widely accepted and effective form of treatment for SDB, and the 
risks associated with its use in this study are reasonable in terms of knowledge gained and 
potential benefits to patients. By its nature, use of PAP therapy may be associated with minor side 
effects. Side effects may cause minor discomfort, especially in a patient who has not previously 
used PAP therapy. In this study, these side effects will not be classified as adverse events unless 
they do not resolve within a reasonable period of time when PAP therapy is discontinued. 
For patients diagnosed with severe sleep apnea and assigned to the usual medical therapy arm of 
the study, the risk of not providing treatment for their sleep apnea is deemed as clinically 
acceptable. Subjects enrolled into the study have been living with untreated sleep apnea, often for 
many years. The study duration (48hrs while in hospital) will not put these subjects at increased 
risk with regard to their sleep apnea; additionally, all subjects in the study will be counseled 
regarding treatment of their sleep apnea when they are discharged from the hospital.  
Subjects should be encouraged to discuss any issues they are having with PAP therapy during the 
study. The investigator should assess for changes in the health or well-being of the subject in 
response to general, non-directed questioning. Side effects should be documented on the site’s 
source documents. Any transient side effects, at a minimum, should be documented in the clinic 
record.  
15.3.2. 
Subject Data Confidentiality 
All information and data collected for the ASAP-HF study concerning subjects or their participation 
in this investigation will be considered confidential. Only authorized personnel will have access to 
these confidential files. All data will be handled in accordance with applicable local laws. 
Authorized FDA personnel or Regulatory Authorities have the right to inspect and copy all records 
pertinent to this investigation. All data used in the analysis and reporting of this investigation will 
be without identifiable reference to specific subject name. 

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16. QUALITY CONTROL AND QUALITY ASSURANCE 
Quality Control is defined as the operational techniques and activities, such as monitoring, undertaken 
within the quality assurance system to verify that the requirements for quality of the study related 
activities have been fulfilled. 
Quality Control should be applied to each stage of data handling to ensure that all data are reliable and 
have been processed correctly. 
16.1. Site Selection 
The sites should have previously participated in clinical studies and must have adequate 
experience, time, staff, and facilities to perform all required duties. Sites must permit clinical trial 
related monitoring, audits, IRB/EC review, and regulatory inspections, providing direct access to 
source data/documents, as appropriate. 
16.2. Polygraphy Data 
Each participating site will be trained and follow the clinical guide for use of the ApneaLink Air 
device and interpretation of data produced in the report. 
16.3. Six-Minute Walk Test 
Each site must demonstrate the ability to follow a standardized protocol for performance of the 
test, including acceptable coaching phrases according to methods described in 6MWT SOP.  
16.4. Echocardiograhpy 
Each site should have access to an experienced sonographer and imaging services in order to 
ensure image acquisition quality. 
16.5. Training 
Each site will be trained on the clinical protocol, study manual, ApneaLink Air and AutoSet 
Instructions for Use, as required. In addition, training on the Data Management System will be 
conducted. If new study staff members are employed at the site after the initiation, experienced 
site personnel must train new employees as noted above and document the training. 
16.6. Site Monitoring 
Each site will have an internal monitor to review the flow of the study and make sure that all 
procedures are being performed in a timely manner. The monitor will verify that standards of 
Good Clinical Practice (GCP) are being followed.  
16.7. Audits and Inspections 
FDA and any other regulatory agencies may request access to all study records, including source 
documents, for inspection and copying, in keeping with Federal regulations.  

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17. RESPONSIBILITIES 
17.1. Clinical Investigator Responsibilities 
With the approval of their institution‘s IRB/EC, qualified investigators will conduct the CAT-HF 
clinical investigation in accordance with the Declaration of Helsinki: “Recommendations Guiding 
Medical Doctors in Biomedical Research Involving Human Subjects”. Each site principal investigator 
and their co-investigators are responsible for the following: 
 
Completion of all required agreements  
 
Screening and evaluation of subjects 
 
Strict adherence to the Clinical Protocol, Study Manual of Procedures and all Federal 
Regulations 
 
Supervising investigational device use and return 
 
Obtaining informed consent prior to study related procedures and the collection of data 
during study and follow-up examinations in a timely manner 
 
Timely reporting of all SAEs and UADEs 
It is acceptable for the site principal investigator to delegate one or more of the above functions to 
an associate or co-investigator, however, the site principal investigator remains responsible for 
proper conduct of the clinical investigation. The investigation is non-transferable to other centers 
attended by the investigator unless prior approval is obtained from the appropriate IRB/EC. 
18. STUDY REPORTS AND PUBLICATIONS 
The Principal Investigator is responsible for preparing and providing the appropriate regulatory 
authorities with clinical study reports according to the applicable regulatory requirements.  

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19. REFERENCES  
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hypertension: the task force for the diagnosis and treatment of pulmonary hypertension of the European 
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Society of Heart and Lung Transplantation (ISHLT). Eur Heart J. 2009;30:2493–2537. 
2 Oudiz RJ. Pulmonary hypertension associated with left-sided heart disease. Clin Chest Med. 2007;28:233–
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3 McLaughlin VV, Archer SL, Badesch DB, et al. ACCF ⁄ AHA 2009 Expert Consensus Document on Pulmonary 
Hypertension: A report of the American College of Cardiology Foundation Task Force on Expert 
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American College of Chest Physicians;  Thoracic Society, Inc.; and the Pulmonary Hypertension 
Association. J Am Coll Cardiol. 2009;53:1573–1619. 
4 Sunil Sharma, Paul Mather etal. Photoplythesmographic Signal to Screen Sleep Disordered breathing in 
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5 Coccagna G , Mantovani M , Brignani F , Parchi C , Lugaresi E . Continuous recording of the pulmonary and 
systemic arterial pressure during sleep in syndromes of hypersomnia with periodic breathing . Bull 
Physiopathol Respir (Nancy) . 1972 ; 8 ( 5 ): 1159 - 1172 . 
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7 Saunders NA , Sullivan CE . Sleep and Breathing . New York, NY : M. Dekker ; 1984 . 
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normal venous return curve . Am J Physiol . 1957 ; 189 ( 3 ): 609 - 615 . 
9 Robotham JL , Rabson J , Permutt S , Bromberger-Barnea B . Left ventricular hemodynamics during 
respiration . J Appl Physiol . 1979 ;47 ( 6 ): 1295 - 1303 . 
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11 Guilleminault C , Cummiskey J , Dement WC . Sleep apnea syndrome: recent advances . Adv Intern Med . 
1980 ; 26 : 347 - 372 . 
12 Arias MA , García-Río F , Alonso-Fernández A , Martínez I , Villamor J . Pulmonary hypertension in 
obstructive sleep apnoea: eff ects of continuous positive airway pressure: a randomized, controlled 
cross-over study . Eur Heart J . 2006 ; 27 ( 9 ): 1106 - 1113 . 
 
                                                          

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13 Tan M, Mather P, Sharma S etal. Treatment of SDB reduces pulmonary pressures in Patients admitted 
with CHF in compliant patients. ATS poster presentation. Am J Respir Crit Care Med 191;2015:A1235 
14 The Criteria Committee of the New York Heart Association. Nomenclature and Criteria for Diagnosis of 
Diseases of the Heart and Great Vessels. 9th ed. Boston, Mass: Little, Brown & Co; 1994:253-256. 
15 Schulz KF, Altman DG, Moher D, for the CONSORT Group. CONSORT 2010 Statement: updated guidelines 
for reporting parallel group randomised trials. Ann Int Med 2010;152. Epub 24 March.