Reducing Heart Failure Re-admissions by Enhancing Sleep Apnea Treatment Adherence
Phase: NA
Conditions: Congestive Heart Failure, Sleep Apnea Syndromes
Sponsor: University of Pennsylvania

 
 
Cover Page 
 
Protocol Title: Reducing heart failure re-admissions by enhancing sleep apnea treatment adherence 
  
December 1, 2018 
 
NCT02312765 
 
 
 

 
3. Research Plan 
3.1. Significance 
3.1.1. The importance of hospital readmissions and congestive heart failure 
Hospital readmissions represent a major clinical setback for patients and impose considerable financial burden 
on the health care system.  Unfortunately, 1 in 12 patients will be re-admitted within 30 days, at an estimated 
societal cost of $16.3 billion (Sommers et al. 2011).  Recognizing the importance of improving readmission 
rates, the 2010 Patient Protection and Affordable Care Act includes the Hospital Readmissions Reduction 
Program, which requires the Centers for Medicare and Medicaid Services (CMS) to reduce payments to 
hospitals with excess readmissions beginning on October 1, 2012 (Centers for Medicare and Medicaid 
Services 2013) (Patient Protection and Affordable 
Care Act  2010).  The program focuses on Heart 
Failure, Acute Myocardial Infarction, and 
Pneumonia-related readmissions.  The penalties 
are considerable:  This year, 2,225 hospitals will 
face penalties estimated at $227 million.  This 
ranges from 1 to 3% of their total Medicare 
patients.  While this may appear as a small penalty, 
it represents a major financial burden because 
hospital profit margins average 4%, thus, as shown 
in the adjacent figure, these penalties, on top of 
private payer penalties, can reduce hospital profit 
margins by 50-100%.  Penalties will increase up to 
5% in 2015, further eroding profit margins for 
hospitals that fail to act to reduce readmissions.     
CMS has decided to focus on heart failure because 
it has the highest readmission rate of any diagnosis 
(24.7%) (Elixhauser et al. 2013).  While health care systems have made several attempts to address 
readmission, cost-effective and meaningful reductions in readmission rates have been “elusive” (Hersh et al. 
2013).  Readmission reduction programs can be broadly divided into predischarge, postdischarge and bridging 
interventions.  Predischarge interventions include medication reconciliation, patient education, and discharge 
planning (Hansen et al. 2011). Postdischarge interventions include follow-up telephone calls, postdischarge 
home visits and patient-activated hotlines (Hansen et al. 2011). Bridging interventions include physician 
continuity (inpatient/outpatient), patient-centered discharge instruction, and transition coaches (Hansen et al. 
2011).  However, none of these individual interventions has been shown to substantially reduce the 30-day 
hospital readmission rate according to one systematic review (Hansen et al. 2011).  While several smaller 
studies have shown a benefit for telemonitoring in heart failure management, the largest study to date of 
telemonitoring in recently discharged heart failure patients failed to show a significant benefit, with readmission 
or death (composite primary end-point) in 52.3% and 51.5% of the telemonitoring and usual care patients, 
respectively (Chaudhry et al. 2010).  It is important to note, however, that this study had several limitations, 
including the use of a relatively simple technology (interactive, telephone based, voice-response system) 
(Chaudhry et al. 2010).   
Taken together, this suggests that there remains significant opportunity to develop more accessible and 
effective telemedicine solutions to reduce hospital readmission rates from heart failure.         
3.1.2. What is the role of sleep apnea in heart failure? 
Sleep apnea is a condition characterized by recurrent cessation of breathing during sleep (Gooneratne et al. 
2012).  Episodes can be either obstructive (in which there is a total cessation of breathing for at least ten 
seconds), central (in which the physiologic drive to breath is absent), mixed (in which episodes may begin as 
central but later assume obstructive characteristics) or hypopneas (in which the volume of breathing is 
reduced, and causes evidence of oxyhemoglobin desaturation or neurologic stress).  It is commonly defined by 
the apnea-hypopnea index, i.e., the number of episodes per hour.  Sleep apnea is extremely common in heart 
failure patients, with prevalences of 51% to 81% (Javaheri et al. 1998) (Herrscher et al. 2011).  For this reason, 
recent heart failure guidelines emphasize the importance of screening and treating sleep apnea (McKelvie et 
al. 2011).  Researchers have also noted an increased risk of death in untreated OSA patients (Javaheri et al. 
2011), with one study observing that none of the OSA-treated CHF patients expired during a mean 2.9 year 
follow-up period (Wang et al. 2007). Treatment of sleep apnea in hospitalized heart failure patients has 

 
demonstrated improvements in systolic function (Khayat et al. 2009).  CPAP therapy has also been found to 
significantly reduce the rate of hospitalization and mortality in heart failure patients (Kasai et al. 2008).  In this 
study, the hazard ratio for hospitalization or death in non-adherent CPAP patients was markedly increased at 
4.02; 95% CI, 1.33 to 12.2 (Kasai et al. 2008). Another prospective study noted profound reductions in 
hospitalization rates for patients with cardiac or pulmonary disorders when treated with PAP (Peker et al. 
1997).  While most of these studies were in patients with obstructive sleep apnea, the landmark CANPAP 
study also showed benefits of CPAP on central sleep apnea (Arzt et al. 2007).  Treated subjects experienced a 
greater increase in left ventricular ejection fraction at 3 months and transplant-free survival than controls.  Of 
note, these benefits only occurred in patients whose sleep apnea was effectively treated with CPAP.  
Furthermore, Khayat and colleagues noted that the presence of central sleep apnea in particular conferred 
greater risk of readmission than any other risk factor in heart failure patients (Khayat et al. 2012).   
Despite this growing body of evidence, sleep apnea is rarely evaluated or treated in heart failure patients:  one 
Medicare database review noted that of 30,719 incident subjects with heart failure, only 545 (2%) received 
sleep apnea treatment (Javaheri et al. 2011).  This highlights that effective diagnosis and treatment of sleep 
apnea could have a major impact on heart failure management.   
The low rate of sleep apnea treatment in heart failure, the fact that heart failure is the number one cause of 
readmission, and the growing financial focus on readmissions creates an ideal opportunity to intervene in a 
focused area, that of sleep-apnea treatment in heart failure.  This targeted intervention has the potential to 
have a high impact on patient care and also be financially sustainable because it would address a very real 
financial concern faced by health care systems, that of avoiding Medicare penalties for readmission. 
3.1.3. What data exists to show that treating sleep apnea can reduce heart failure readmissions? 
Isolated case reports have suggested that acute treatment of sleep apnea in hospitalized patients with heart 
failure can be of significant benefit (Deswarte et al. 2008).  This prompted the University of Pennsylvania Sleep 
Center to establish several years ago a program that allows in-patients on the cardiology service to be 
evaluated with a polysomnography to diagnose sleep apnea and shortly thereafter receive sleep apnea 
treatment using an auto-titrating PAP machine, all during their initial hospitalization.  The patient can then 
continue to use the PAP unit at home.  These units are linked via wireless modem to allow real-time monitoring 
of PAP therapy in the hospital and while at home.  This prompt diagnosis/treatment program has since been 
adopted in the past year by other area hospitals and is becoming a model for nationwide care delivery.     
We have conducted a preliminary analysis of the first 106 consecutive patients from the in-patient program. 
These 106 patients were on the Hospital of the University of Pennsylvania Cardiology units for congestive 
heart failure (87.4%, of which 53.3% had New York Heart Association Class 3 and 41.1% had Class 4 heart 
failure) or other cardiovascular conditions.  Of these 106 patients, 81 (78%) were found to have sleep apnea 
on their diagnostic in-hospital sleep study; this is consistent with findings from other research that suggest a 
high prevalence of sleep apnea in heart failure patients (Javaheri et al. 1998) (Herrscher et al. 2011).  Of these 
patients, 80% (65/81) had predominantly obstructive sleep apnea and 20% (16/81) had predominantly central 
sleep apnea.  Patients were then started on PAP therapy the next night while in the hospital and continued on 
PAP therapy at home.  
Readmission and Emergency Department 
visit rates were then monitored as the primary 
outcome; this occurred in 16.2% of patients 
within 30 days after discharge. Patients were  
divided into PAP full users (adherent  >4 
hours of use a night), partially PAP users 
(adherent 0 to 4 hours per night) and non-
users.  The readmission rates are shown in 
the related Figure.  The most striking finding 
is that while 29-30% of the partial users and 
non-users were re-admitted within 30 days, 
none of the PAP full users were re-admitted 
(p=0.025).  Also of note, only 34% of the 
discharged heart failure patients were full 
users of PAP—the majority of discharged 
patients were either non-users (30%) or 
partial-users (36%); this highlights the need to 
develop interventions to improve PAP 

 
adherence.  The manuscript related to these findings is accepted for publication in the Journal of Clinical Sleep 
Medicine pending revisions (peer-reviewed journal). 
While these findings are provocative, it is important to highlight the numerous limitations of the above 
preliminary data.  First, this is a naturalistic quasi-experimental study—the patients were not randomized to 
PAP or sham-PAP.  Second, the study has a small sample size.  Third, echocardiographic data and other 
biomarker data was not available to examine physiologic mechanisms. Fourth, follow-up readmission data and 
PAP adherence data was only available in 56 out of the 81 patients.  Despite these limitations, we believe the 
above data suggests a possible role for sleep apnea treatment for reducing heart failure readmissions. 
What could explain this significant reduction in readmission rates?  We hypothesize that there are two main 
avenues of benefit.  First, treatment of sleep apnea has been shown to improve cardiac function in heart 
failure:  one randomized trial demonstrated an increase in the left ventricular ejection fraction from 25.0+/-2.8 
to 33.8+/-2.4 percent, reduced the left ventricular end-systolic dimension from 54.5+/-1.8 to 51.7+/-1.2 mm  
and other benefits (reduced heart rate and blood pressure) (Kaneko et al. 2003).  Second, it is likely that PAP 
adherence is also linked to general medication adherence.  Research conducted at the University of 
Pennsylvania has shown that PAP adherence correlates with medication adherence (Platt et al. 2010).  
However, this has not been noted in all studies (Villar et al. 2009).   
Taken together, this suggests three intriguing possibilities.  First and foremost:  treatment of sleep apnea may 
be of significant benefit in reducing readmission rates.  Second, it is possible that PAP adherence could be a 
surrogate measure of general medical adherence.  Since PAP adherence is being monitored by available 
usage trackers built into the current PAP devices, this provides a low cost, seamless and wireless means of 
identifying patients at general increased risk for non-adherence.  Thus a patient flagged as being non-adherent 
with PAP should also be queried for general medication and dietary adherence.  Third, there remain significant 
problems with overall PAP adherence with rates as low as 34%—interventions that could improve adherence, 
such as the proposed study, could have a meaningful impact.    
3.1.4. What is the importance of oxyhemoglobin saturation and why should we measure it? 
While the acute stress of an apnea or hypopnea event is important, research suggests that hypoxia may have 
a greater impact as demonstrated by a stronger association with brain (B-type) natriuretic peptide (BNP), a 
measure of cardiovascular and hemodynamic stress (Gottlieb et al. 2009). This is of particular importance 
because, while the current PAP treatment devices have robust internal monitoring capabilities including hours 
of use, they do not routinely include capturing oxyhemoglobin saturation data.   
Recently, new technology has been developed (iHealth oximeter) that can connect via a Bluetooth wireless 
interface to provide real-time oximetry data.  We will propose in Phase 1 to modify the AirCare system to bring 
in this real-time at-home oximetry data so that we can derive a more accurate and useful measure of PAP 
effectiveness in treating sleep apnea in heart failure patients.  This represents a substantial innovation in care 
delivery for sleep apnea. Currently, at-home oximetry can be obtained by ordering a nocturnal oximetry 
through a patient’s durable medical equipment provider (DME).  However, in actual clinical practice, these are 
difficult to obtain largely due to inadequate reimbursement by insurance providers.  For example, Medicare 
currently reimburses as little as $13.29 for an overnight oximetry study in the patient’s home (Beauliea 2012).  
Most DME companies lose income on nocturnal oximetry and many refuse to provide this service (Beauliea 
2012).  At the Penn Sleep Center, we are unable to easily obtain overnight oximety on patients at home using 
currently available pathways, thus creating significant challenges for patient care.   
3.1.5. What are the barriers to treating sleep apnea? 
Treatment of sleep apnea can be achieved through positive airway pressure therapy (PAP), oral appliances 
(these take 2-3 months to custom manufacture), upper airway surgery (removal of the posterior portion of the 
tongue, tonsils, soft palate, and/or osteotomy cuts in the mandible to advance the mandible along with the 
tongue), implanted nerve stimulators (in development), weight loss, or oral pressure therapy (oropharyngeal 
vacuum system) (Gooneratne et al. 2012) (Aurora et al. 2010) (Chan et al. 2007).  PAP therapy exists in a 
variety of forms, such as continuous positive airway pressure (CPAP), auto-titrating positive airway pressure 
(APAP), bilevel positive airway pressure (bilevel or BiPAP).  They all have in common the use of a face mask 
applied with an air-tight fit to either the nose, or nose/mouth, through which positive airway pressure ranging 
from 5 to 20 cm H2O is applied (on average).  PAP is the most effective treatment option for sleep apnea and 
is able to fully treat sleep apnea in over 85% of patients (Gooneratne et al. 2012) (Epstein et al. 2009).   
Despite having a highly effective therapy that can be initiated promptly, adherence to PAP is a major limitation 
as noted in a review conducted recently by our group (Sawyer et al. 2011).  There are several reasons why 
using PAP is so challenging.  More significant has been the overall difficult of learning how to effectively apply 

 
the mask to minimize mask leak and maximize patient comfort.  Generally, patients are shown how to apply 
the mask during a 30-45 minute demonstration session during the day when they first receive their PAP 
machine from a Durable Medical Equipment (DME) provider.  Attention to detail and education varies widely, 
with some DME providers simply dropping the PAP equipment and mask off at the front door, while others 
make an effort to demonstrate use and train the patient.  However, due to significant cut-backs in Medicare 
reimbursement rates to DME, the level of service they provide has deteriorated over the past year.  Fewer and 
fewer DME companies now make house calls to patients after the initial visit, requiring instead that the patient 
come to the DME office which may be located far from their home.  The DMEs also offer on-call respiratory 
technician services via telephone, but response times and service quality vary considerably with over 70% of 
patients in our sleep clinic voicing dissatisfaction with the level of support provided by their DME.  Physician 
offices can also assist patients with their PAP machines and masks, however, most physician visits are 15-20 
minutes, thus there is limited time to adequately instruct the patient in how to properly apply the mask.  Waiting 
delays for follow-up sleep physician appointments can average 15-90 days (based on review of Penn Sleep 
Clinic records).     
Most strikingly, there is no system in place to provide patients with assistance at night, when they are actually 
trying to use their machine at home.  This glaring omission in care support will be addressed by the current 
proposal.  Indeed, when directly asked what service patients would most appreciate, access to assistance at 
home at night is ranked as the highest priority based on surveys conducted by our clinic.  
3.1.6. How can the AirCare System improve PAP adherence and reduce readmission rates? 
The transition to self-care at home after being discharged from an acute care facility is one the most difficult 
steps in a patient’s recovery. Patients are provided with an overwhelming amount of information at discharge, 
most of which is incomprehensible, difficult to follow, and not fully absorbed. In order to be engaged, patients 
must have a resource to connect to someone knowledgeable about their disease and their particular priorities 
and can help them through the vulnerable few weeks right after they are discharged.     
AirCare systems offer an inexpensive and easy-to-use solution to prevent unnecessary readmissions though 
patient checklists, symptom reporting, and mobile video with care providers, such as trained medical 
assistants, nurses and other care providers.  In addition, AirCare risk categorizes patients into high, medium 
and low risk (red, yellow or green statuses) automatically, which helps us focus resources appropriately. 
AirCare manages readmissions by offering providers the opportunity to remotely monitor patients as well as 
virtually connect to patients through phone and secured video chat.  
AirCare Tablet:  At the touch of a 
button, care providers are able to 
connect with patients via laptop, 
tablet or phone to provide seamless 
transitions of care, virtual monitoring 
of compliance, targeted patient 
education, and individualized care 
plans.  To use AirCare Tablet, 
patients need an Android tablet with 
4G data connection or a computer 
with a webcam, Google Chrome and 
high speed internet connection.  For 
patients without home computer 
access, AirCare has established 
relationships with mobile providers 
(AT&T, T-Mobile, etc.) and has 
negotiated agreements to provide 
tablets to patients.  Providing patients 
with a preloaded, up-to-date tablet 
with AirCare Tablet as the primary 
application maximizes ease of use 
and simplifies the process of 
contacting a health care practitioner. 
AirCare Voice:  AirCare Voice is an automated call system that places calls to patients each morning with 5 
customized questions, which the patient can respond to via keypad. This patient data is sent into the same 

 
algorithm as AirCare Tablet, allowing for risk stratification and nurse phone follow-up. This system is more 
appropriate for patients who prefer phone communication rather than tablet communication.    
The system offers several unique benefits for improving sleep apnea adherence as well.  First and foremost is 
access to care providers: the AirCare system can be used to provide patients with at-home assistance in the 
evening when they are actually using their PAP therapy.  Currently, there is no available solution to provide 
patients with help during this period.  Patients can use the AirCare system to contact a sleep technician 
working the night shift in the sleep lab to receive immediate help if they are having difficulty applying the mask, 
adjusting the device settings or facing other technical challenges.  The video chat feature is particularly helpful 
in this regard.  Second, AirCare is an ideal patient education tool to provide patients access to easy-to-
understand video educational content and other instructional material. We propose in Phase 1 to build into the 
AirCare system educational material related to sleep apnea treatment developed by the Penn site.  Third, 
AirCare Tablet provides health reminders regarding PAP adherence and healthy behavior, including sleep 
habits, through tablet notifications. AirCare Voice provides these notifications through automated texts and 
calls. Together, these tools allow AirCare to maximize patient engagement; these will be extended to include 
sleep apnea.  In addition, caretakers are able to become actively involved through AirCare.  If permission is 
granted by the patient, the caregiver can check on PAP usage or daily weight, etc. This caregiver involvement 
can help the engage the patient’s support system in their care, which can also contribute to reducing 
readmissions.   
3.2. Innovation 
The current proposal is the first targeted solution that seeks to reduce heart failure readmissions through 
improved sleep apnea treatment adherence by allowing patients to have ready access to at-home assistance 
with their PAP throughout the night. Furthermore, we propose to extend these successes in the proposed SBIR 
by adding several additional features. 
Phase 1:  We will develop new technology to incorporate real-time at-home pulse oximetry data.  This will allow 
health care providers to have a highly relevant, non-invasive measure of sleep apnea efficacy that extends 
beyond currently limited options.  In addition, we will use structured interviews to identify key areas for 
educational intervention and develop relevant educational material to embed within the AirCare system for 
patient access at home.  Of particular importance to sleep apnea care, we will use the Phase 1 portion of the 
study to build in links to an on-call sleep technician.  The Penn Sleep Center currently has eight sleep 
technicians working each night supervising sleep studies.  The majority of their active duties occur from 6 PM 
to 9 PM as they connect patients to the in-lab sleep study equipment.  After 9 PM until 6 AM the next morning, 
they are generally passively observing patients on the monitors or scoring sleep studies from the prior nights.  
This creates an available, trained sleep technician resource that could assist patients at home using the 
videoconferencing features of the AirCare Tablet from 9 PM to 6 AM.  Since these staff are already working, 
they can provide assistance to patients affiliated with the sleep clinic without additional financial cost to the 
sleep clinic.  Furthermore, since they are health care employees of the sleep clinic that also takes care of the 
patient, they are allowed to view patient healthcare data. 
Phase II:  We will further integrate the AirCare system with the PAP device internal adherence data, creating a 
directly linked comparison between PAP and a key outcome—nocturnal pulse oximetry.  We will develop risk 
classification algorithms to interpret the real-time oximetry and PAP data and make it available to patients and 
providers through the AirCare system.   
We will then test the AirCare system in a large demonstration randomized controlled trial. This will be the first 
randomized trial examining the impact of enhanced sleep apnea treatment on 30-day hospital readmission 
rates. 
An additional key innovation is the financial model supporting this intervention.  Currently, sleep apnea care is 
a fee-for-service model that only adequately reimburses physician or nurse practitioner time.  Reimbursements 
for Durable Medical Equipment (DME) companies have declined sharply, with many companies reducing their 
patient support services in response.  Past efforts to develop PAP adherence promoting interventions have not 
been routinely adopted because they were not reimbursed by payers.  The AirCare solution takes a different 
approach:  By demonstrating a financial benefit to hospitals, the AirCare solution can directly approach health 
care systems to cover the cost of the service.  This will allow for a much more rapid uptake of the service than 
traditional biomedical innovations which require obtaining Medicare approval for new billing codes, a process 
that can take several years at best and even then may not be adequately reimbursed or approved by other 
payers.  Additional details of this financial model, the first proposed in the sleep apnea field that directly 
approaches hospital systems, is provided in the Commercialization Plan section.   

 
3.3. Approach 
This project represents a partnership between AirCareLabs and the University of Pennsylvania Sleep 
Disorders Center.  AirCareLabs has developed an innovative technology platform that focuses on the 30-day 
readmission period to create a seamless interface for patient-provider interactions and monitoring of disease 
metrics.  The Penn Sleep Center is an internationally recognized leader in the field of sleep medicine, with over 
15 active sleep medicine clinicians and an in-patient sleep consult service that, in preliminary data, has shown 
that sleep apnea treatment for heart failure patients has the potential to reduce readmission rates.  However, 
the major limitation of the existing in-patient sleep consult service is the low adherence rate (approximately 
30%) post-discharge, a limitation that can be effectively addressed using the AirCareLabs solution; this is the 
core proposition of the current protocol. 
The proposed project Phase 1 includes the following key components:  1) Structured interviews with users/care 
providers; 2) Creating educational content; 3) Developing problem resolution care pathways; 4) Integration of 
Oximeter data;.  The proposed project Phase II includes the following key components: 1) Integration of PAP 
adherence data; 2) Revising educational content and care pathways; 3) Developing risk classification criteria; 
and 4) Conducting a large randomized clinical trial to demonstrate effectiveness.  These elements are 
described in more detail below. 
We propose to utilize the Fast Track mechanism because the compelling preliminary data suggest the potential 
for a significant improvement in patient outcomes; all the elements of the program are in place to allow for 
implementation; and the rapid evolution of the competitive landscape relies upon a first-to-market approach to 
gather crucial market share to improve commercialization prospects. 
3.3.1. Phase 1 Plan 
3.3.1.1 Task 1.1:  Structured interviews 
 
We will conduct one-on-one interviews with key stakeholders—patients and sleep medicine providers 
(physicians/nurse practitioners, sleep study technicians).  These interviews will be used to maximize usability, 
resolve potential problems with the user interface, and identify key educational content materials.   
The interviews will be conducted by a team consisting of one interviewer (Dr. Gooneratne and/or Mr. Zeng) 
and a note-taker; this will allow the interviewer to focus on guiding the discussion.  Interview participants will be 
compensated for their time at a rate consistent with their usual hourly salary. The general interview framework 
is as follows:  1) Open discussion during which the user/provider will be asked to discuss their understanding 
of heart failure, sleep apnea, and challenges associated with sleep apnea treatment, as well as the current 
solutions they have attempted to use; 2) A demonstration of the AirCareLabs system, including patient survey 
feature, assistance request mechanism, and videochat features; 3) Semi-structured interview of their 
experience with the AirCareLabs system, suggested areas for improvement, and interest in using the system; 
and 4) They will also be asked to identify areas which they feel would most benefit from educational videos or 
additional documentation/description, and common problems that merit the development of clinical care 
pathways. 
The general structure above will be applied to the following specific user/provider groups:  
Patients:  We will conduct interviews with three patient groups at various points along the hospital timeline:  1) 
inpatients, 2) recently discharged patients and 3) patients at 4-6 months follow-up.  We have elected to take 
this approach because the specific challenges a patient faces at each of these time points may differ, and if we 
wait until the end of the study to interview the patients, they may no longer recall the problems they faced 
earlier on, for example, during their hospital admission.  We will interview at least 10 patients within each of 
these three groups.  Eligible patients will be those admitted with a heart failure exacerbation diagnosis as their 
primary diagnosis or active heart failure during their hospital course that requires treatment modification.  They 
must also be newly diagnosed with sleep apnea during their admission.  The in-patient group will be 
approached shortly prior to their anticipated discharge date.  The recently discharged patients will be 
interviewed 1-2 weeks post discharge, and the 4-6 month follow-up group will be contacted at 6 months for 
interviews. 
Sleep Technicians: The Sleep Technicians will be responsible for providing overnight assistance to patients 
that are having difficulty using their PAP at home.  The Penn Sleep Center employs over 30 sleep technicians 
that staff the 28 sleep study beds at 6 different locations.  We will randomly invite them to participate and seek 
to conduct at least ten interviews using the framework described earlier.      

 
Sleep medicine providers (physicians, nurse practitioners, nurses, medical assistants): The sleep medicine 
staff that provide day-to-day care for patients will be randomly selected for interviews, with at least 15 
interviews, of which a minimum of seven will be with sleep medicine physicians.     
3.3.1.2 Task 1.2: Develop educational content 
 
Based on the input provided during the one-on-one interviews, we will identify areas of focus that warrant 
educational videos and brochures.  Sample topics include the etiology of sleep apnea, how PAP therapy 
works, tips for applying masks, and dealing with mouth/nose dryness.  Dr. Gooneratne will produce at least five 
educational videos of an average duration of ten to fifteen minutes, and ten brochures that can be viewed from 
the AirCare system.  The Penn Sleep Center has a Sleep Education Unit that will assist with the production of 
the educational content.  This educational unit currently conducts live Webinars, has produced educational 
videos for display in the patient waiting area, and is active in CME events. 
3.3.1.3 Task 1.3:  Problem resolution care pathways 
 
The sleep medicine providers and sleep technicians will be contacted by patients through the AirCareLabs 
system for a variety of problems faced by patients as they start using PAP therapy.  Based on the input from 
the one-on-one interviews, Dr. Gooneratne will develop clinical care pathways for resolving the most common 
problems using evidence-based practices.  This will allow for standardized care across different providers.  For 
example, if a patient complains of nasal congestion, one possible set of recommendations would be: 1) three 
day trial of saline nasal spray; 2) if unsuccessful, five to seven day trial of ipratropium nasal spray; 3) if 
unsuccessful, review patient nasal spray technique, etc.   
3.3.1.4 Task 1.4:  Integration of oximeter data 
 
Inclusion of real-time, continuous pulse oximetry data will allow for monitoring a key efficacy measure for 
PAP:  oxyhemoglobin saturation.  We will use the iHealth oximeter because of its small size, battery life, low 
cost, and ability to interface wirelessly via Bluetooth to the AirCareLabs tablet.  The unit has an oxyhemoglobin 
saturation measuring range of 70-99% with an accuracy of ±2% in that range.  During Phase I, we will use the 
available iHealth open API to establish a connection between the AirCareLab system and user data from the 
oximeter.  The system establishes on OAuth client_id and client_secret for each user. The OpenApi can then 
make requests to the iHealth API Endpoints with the authenticated OAuth credentials.  The oximeter itself can 
store 100 data points, at which time it can send the data, via Bluetooth to the AirCareLab tablet, which will then 
transmit it via the cellular network to the iHealth server.  This data can then be shared with the AirCareLab 
server using the iHealth OpenApi.  The oximeter data can then be queried by users, such as the sleep 
technician or sleep medicine provider, who wish to monitor the efficacy of the PAP therapy.  This powerful 
technology will allow the sleep medicine team to move beyond simple PAP-derived apnea-hypopnea index 
values and instead assess the efficacy of treatment on the key endpoint of oxyhemoglobin saturation in a real-
time application.  We anticipate that the oximeter will be used on a nightly basis for the first week, then as 
needed if there are continued patient symptoms or any deterioration in the patient’s clinical condition. 
3.3.1.5 Timeline for Phase 1 Tasks: 
Tasks 
Month 1 Month 2 Month 3 Month 4 Month 5 Month 6 
Task 1:  Structured interviews 
 
 
 
 
 
 
Task 2:  Educational Content 
 
 
 
 
 
 
Task 3:  Problem resolution scripts and Staff 
training 
 
 
 
 
 
 
Task 4:  Oximetry API connection 
 
 
 
 
 
 
 
3.3.1.6 Milestones for the Phase 1 project: 
1. Structured interviews with users/care providers:  Successfully conduct 30 patient interviews, 10 sleep 
technician interviews, and 15 sleep medicine provider interviews (at least seven with a sleep medicine 
physician).      
2.  Educational content:  We will create a minimum of five demonstration video clips and ten step-by-step 
brochures that explain PAP use, mask application, and device care, based on guidance received during the 
structured interviews. 
3. Development of at least ten care pathways to guide sleep technicians and medical assistant staff to 
assist patients resolve common PAP issues based on focus group work as well as staff training in 
implementing these scripts. 
4. Oximetry data integration using the iHealth API:  Successful oximetry data collection will be defined as 
1a) maintaining a wireless connection continuously between the AirCare app and the iHealth oximeter for at 

 
least 75% of the study night and 1b) successful transfer of the oximetry data to the central server in 30 minute 
increments in at least 90% of the cases.   
3.3.2. Phase 2 Plan  
The goal of Phase 2 is to integrate PAP device data, refine the educational content, develop risk classification 
content and conduct a randomized controlled trial of the AirCareLab system in a target population of 240 
patients. 
3.3.2.1 Task 2.1:  PAP device data 
 
The PAP devices collect hours of use, estimates apnea-hypopnea index through flow monitoring, and 
mask leak data on a nightly basis.  This data is transmitted wirelessly by modems attached to each unit that 
connect to the cellular phone network.  The large majority of Durable Medical Equipment (DME) providers offer 
this service since the insurance companies generally require documentation of adherence during the first three 
months of use to justify continued insurance coverage.  This data is stored in a central server maintained by 
each of the major PAP equipment manufacturers, and is shared with the patient’s providers through a web 
portal data review system.  The companies also delivery this data in .csv files on a daily or weekly basis to 
provider groups, such as the Veterans Affairs administration, large group practices such as the Penn Sleep 
Center or health systems.  The general data format is one row per night of use.  During Phase 2, we will 
integrate this data into the AirCareLabs workflow and make it available to patients and providers directly 
through the AirCare system.  We have elected to perform this in Phase 2 instead of Phase 1 because there are 
already several commercial platforms that allow for patients and providers to view their PAP-device data, 
therefore this offers less of a competitive advantage than direct integration of oximetry data, which we have 
therefore prioritized to Phase 1. 
3.3.2.2 Task 2.2:  Refine educational content 
 
The Educational content created in Phase 1 will be incorporated.  Based on the feedback and usage rates 
of this content, we can then further refine the material.  This may include shortening content, adding additional 
material in a specific section of an existing video/document, or creating new content if necessary.  We will be 
adding a motivational piece, whereby a member of our research staff will contact patients to evaluate their 
progress and issues while using the PAP unit.  Patients will be called on Day 1, 2, 5, 7 and weeks 2, 3, and 4. 
 
3.3.2.3 Task 2.3:  Develop risk classification criteria 
 
One of the strengths of the AirCare system is the ability to query the user data on a daily basis to identify 
patients at high risk for readmission.  For example, patients that show low rates of PAP use, increased weight 
gain, or increased levels of dyspnea, may be at high risk of readmission.  The system can generate alerts to 
health care providers to notify them of this risk so that they can intervene.  We will review the symptom data 
collected during the focus groups to derive preliminary risk classification criteria for non-adherence to PAP 
therapy for sleep apnea.  Candidate targets include low self-report rates of PAP use (such as less than 4 times 
a week), and persistent oxyhemoglobin desaturations despite PAP therapy (such as persistent desaturations to 
<90% at night). 
3.3.2.4 Task 2.4:  Randomized Controlled Trial 

 
 
The majority of effort during Phase 2 will be devoted to conducting a randomized controlled trial to assess 
the effectiveness of the AirCareLabs system for reducing 30-day readmission rates in a cohort of    heart failure 
patients with sleep apnea.  This study will be conducted at the University of Pennsylvania Health System under 
the guidance of Dr. Gooneratne (sleep medicine), Schwab (sleep medicine) and Goldberg (cardiology), with 
assistance from Mr. Zeng and the AirCareLabs team.  The proposed study flowchart is shown below. 
 
3.3.2.5 Study Inclusion/Exclusion Criteria: 
 
We have attempted to minimize the study inclusion/exclusion criteria in order to maximize study 
generalizeability. Individuals must meet the following inclusion criteria prior to study enrollment: 1) Acute heart 
failure exacerbation requiring hospitalization (primary diagnosis) or admitted for another indication, but whose 
hospital course has become complicated by heart failure exacerbation.  2) Diagnosis of sleep apnea: 
Established by an apnea-hypopnea index (AHI) ≥ 5 events/hr consisting of predominantly obstructive apneas 
and hypopneas on full-night portable in-hospital polysomnography.  This is the commonly used clinical criteria 
for sleep apnea in the setting of underlying cardiac disease (American Academy of Sleep Medicine 2005) 
(Gooneratne et al. 2012).  3) Age ≥ 18 years (see section on “Inclusion of Children”). 
Individuals will be excluded from the study for the following reasons: 1) Inadequate sleep apnea treatment with 
PAP alone: (with up to 2 LPM oxygen) Unable to be adequately treated with PAP to a target AHI<15 events/hr 
and oxyhemoglobin desaturation nadir >90% and clinical improvement. 2) Unable to perform tests due to 
inability to communicate verbally, inability to write and read in English; less than a 5th grade reading level; 
visual, hearing or upper extremity motor deficit (e.g., previous stroke that prevents patient from using PAP 
treatment).  
3.3.2.6 Subject recruitment:   
 
As part of their routine clinical care, patients with active heart failure exacerbation will be evaluated by the 
sleep in-patient consult service and undergo a portable sleep study. Those with newly diagnosed sleep apnea 
that elect to start PAP therapy and are adequately treated with PAP therapy will be eligible to participate in the 
Phase 2 clinical trial.  They will undergo an informed consent session using an IRB-approved consent 
document.  Based on our prior experience, we anticipate that approximately 75% will agree to participate. Thus 
to enroll 240 participants, we must approach 320 heart failure patients with diagnosed sleep apnea.  Our 
preliminary data demonstrated that approximately 80% of admitted heart failure patients have sleep apnea, 
thus 400 heart failure patients will need to be screened for sleep apnea.  The sleep disorders consult service 
has 10 new consults each week from the cardiology inpatient units for sleep apnea screening, thus 
approximately 500 new consults per year; we anticipate this volume will be adequate to enroll the required 
cohort for the Phase 2 study. 
We will also recruit subjects from the Presbyterian and Pennsylvania Hospitals, following the same recruitment 
strategy.  We will enroll subjects with a previous OSA diagnosis, who were previously unable to use CPAP.  
We will also submit a query to the Penn Data store, for de-identified data for the following: age, BMI, gender, 

 
dx of hypertension and CHF, in an effort to expand our recruitment sources.  We are also adding an additional 
recruitment site; Washington University at St. Louis, (WASU), site PI: Dr. Luqi Chi.  This site will follow the 
same recruitment strategy as Presbyterian and Pennsylvania Hospitals. 
3.3.2.7 Study Procedures:   
 
After completing the informed consent process, study participants will complete the following study 
questionnaires (copies are provided in the Appendix): a) Self-Efficacy Measure for Sleep Apnea (Weaver et al. 
2003), b) Self-Care of Heart Failure Index (Riegel et al. 2004), c) RAND Medical Outcomes Study Short Form 
(SF-36) (Ware et al. 1992), d) Epworth Sleepiness Scale (ESS) (Johns 1993). In addition, the medical chart will 
be abstracted by the study research coordinator to complete the Cumulative Illness Rating Scale (CIRS), 
gather demographic data, medications and other relevant covariates (Miller et al. 1992).  They will then be 
randomized in a 1:1 ratio to either the AirCareSystems tablet or standard care as described below:   
AirCareSystems Group:  Study participants in this arm will receive a tablet computer with a pre-installed 
AirCare application.  The tablet will be locked to prevent other usage.  All data from previous users will have 
been wiped from the tablet.  The patient will be instructed in the use of the tablet, and will be encouraged to 
view the installed educational content created in Phase 1.   
At the time of discharge, the study participants will leave the hospital with the PAP unit, the tablet computer 
and an iHealth oximeter. (In the event the patient is discharged before their PSG, they will use the Embletta at-
home sleep device to determine eligibility).  At home, they will be asked to complete daily, brief questionnaires 
about their symptoms.  They can also use the tablet to submit queries to request assistance with their sleep 
apnea care.  These queries will be answered during the daytime by the day shift sleep technicians or sleep 
medical assistants according to the standardized care pathways developed earlier.  At night, they will be 
answered by the sleep technicians staffing the 6 active sleep labs (operating seven days a week on all days 
except national holidays).  They will also use the iHealth oximeter on a nightly basis for the first week, then on 
an as-needed basis thereafter depending upon their symptoms or requests from care providers.  It is 
anticipated that the average study participant will make 2-5 night-time assistance requests, and 3-7 daytime 
assistance requests.  The Risk Classification criteria developed in Task 2.3 will be applied to identify study 
participants who are at high risk of non-adherence or readmission. 
PAP adherence will also be tracked using the built-in device PAP units. Hospital readmissions, ER visits and 
other doctor visits will also be recorded. 
At the end of the first month of treatment, study participants will be asked to return their tablet and iHealth 
oximeter.  They will also be asked to complete the same battery of study survey instruments they completed at 
the initiation of the study protocol; this will be repeated at six-month follow-up as well. 
Standard Care Group:  Study participants in the standard care arm will be asked to complete the same survey 
instruments shortly prior to discharge.  They will leave the hospital with their PAP unit.  Out-patient support will 
be provided by the study participant contacting their Durable Medical Equipment (DME) provider for assistance 
or their sleep medicine provider through the sleep clinic.  At the end of the first month, and again at 6 months, 
they will be asked to complete the same battery of survey instruments they completed at the initiation of the 
study protocol.  PAP adherence, hospital readmissions, ER visits and other doctor visits will also be tracked 
3.3.2.8 Data Analysis 
 
Descriptive Comparisons Between Intervention Groups at Baseline:  Descriptive analyses will be 
performed in order to characterize the two study groups (AirCare and Standard Care) and to confirm that the 
randomization resulted in no clinically significant group differences at baseline in demographic, sleep, and 
other parameters. If the groups differ with regard to baseline variables and these variables are found to have 
significant associations with outcomes, secondary analysis of covariance will be used to investigate the degree 
to which estimated relative efficacy depends on these baseline differences.  
 
Hypothesis:  The AirCareLabs system will improve PAP adherence post-discharge relative to standard 
care.  Statistical analysis method:  PAP adherence will be defined as at least 4 hours of use per night on at 
least 70% of the study nights (thus, in a typical 30 day month, the study participant will have used it 21 nights 
for greater than 4 cumulative hours each night); this is consistent with Medicare PAP usage criteria.  We will 
review the PAP adherence downloads, which provide an objective measure of adherence, to determine what 
percentage of patients in each study arm (AirCare vs. Standard Care) met the adherence criteria (i.e., a patient 
may be either adherent or non-adherent with PAP).  We will utilize a chi-square frequency comparison for this 
primary analysis.  

 
3.3.2.9 Sample Size Analysis 
 
The study statistical power will be based on a two-sided Type 1 error rate of 0.05, and a Type 2 error rate 
of 0.20; these are commonly used criteria for study power calculations.    
Hypothesis:  We anticipate, based on our preliminary data, that 30% of patients will be fully adherent to PAP 
therapy (use >4 hours per night for >70% of the month).  An improvement in adherence to 50% would 
represent a clinically meaningful change.  Using a power analysis based on the chi-square frequency 
comparison, we anticipate that a sample size of 93 study participants per group will provide an adequate study 
power.  We will increase this by 30% to factor in study attrition or loss to follow-up, thus a sample size of 120 
would be adequate. 
3.3.2.10 Timeline for Phase 2 Tasks      
Tasks 
Month  
1-2 
Month 
3 
Month 
4 
Month 
5-17 
Month 
18-19 
Month 
20-23 
Month 
24 
Task 1:  PAP data integration 
 
 
 
 
 
 
 
Task 2:  Refine Educational Content 
 
 
 
 
 
 
 
Task 3:  Risk Classification Criteria 
 
 
 
 
 
 
 
Task 4:  Study IRB approval 
 
 
 
 
 
 
 
Task 5a:  Randomized Clinical Trial:  Enrollment period 
 
 
 
 
 
 
 
Task 5b:  Randomized Clinical Trial:  6-month follow-
up period 
 
 
 
 
 
 
 
Task 6:  Data analysis/manuscript generation (30-day 
readmission analysis) 
 
 
 
 
 
 
 
Task 7:  Data analysis/manuscript generation (6-
month follow-up analysis) 
 
 
 
 
 
 
 
 
3.3.2.11 Milestones for the Phase 2 project: 
1.  PAP data integration:  Successful oximetry PAP collection will be defined as transfer of the PAP data 
to the AirCareLabs central server in at least 90% of the study days. 
2. Refine educational content:  Study participant will be asked to rate their satisfaction with the 
educational content using visual analogue scales.  The educational content will be revised during Task 
2.2 in Phase 2.  These visual analogue scales will then be repeated during the larger randomized trial 
(Task 2.4 in Phase 2).  Successful completion of this task will be defined as a 20% improvement in 
study participant satisfaction scores after revising the educational content    
3. Risk Classification Criteria:  A minimum of ten risk classification criteria will be developed based on 
review of the data.  In our preliminary study, we noted that approximately 70% of study participants 
were non-adherent to PAP therapy.  Thus, successful completion of this milestone will also include the 
requirement that the ten risk classification criteria flag at least 60-70% of patients as being at risk for 
non-adherence with PAP therapy.   
4. Randomized controlled trial:  Successful completion of a randomized controlled trial of 240 study 
participants, with over 90% study questionnaire data completion.  
3.3.3. Known limitations 
The experience gathered by the study team implementing the AirCareLab system, as well as the Penn Sleep 
Center through their sleep consult service, has allowed us to address many of the potential barriers to 
implementing this proposal.  Specific issues that warrant consideration include the following: 
Is a typical heart failure inpatient admission long enough to allow for sleep apnea diagnosis and treatment 
initiation?  Our preliminary data showed an average admission duration of 13.0 (+/-8.7) days—we noted that 
this was ample time to allow initiation of PAP therapy. 
Will other hospitals initiate this program?  The area of acute sleep apnea treatment in hospitalized patients is a 
“hot topic” in the field right now.  For example, the American Society of Anesthesiologists has developed a 
sleep apnea screening tool for pre-operative evaluation, thus highlighting the growing interest in identifying 
sleep apnea in hospitalized patients.  Several studies have linked sleep apnea to adverse outcomes in 
hospitalized patients and health systems have been sued for failure to diagnose sleep apnea in hospitalized 
patients.  We anticipate that by the time this SBIR proposal is finished, the majority of hospitals will offer some 

 
form of rapid sleep apnea diagnosis service.  Several hospitals in the Philadelphia area alone, for example, 
have initiated an in-patient sleep consult program in the past year.  However, all of these programs face the 
same hurdles faced by the Penn Sleep Center:  low PAP adherence rates post discharge.  Improving post-
discharge PAP adherence rates is thus the target goal of the current SBIR proposal. 
3.4. Summary 
Hospital readmissions, in many cases, represent a failure of the health care system.  Patients, prior to 
discharge, have had their cardiac status optimized and are in a controlled environment where the hospital staff 
can help to educate and prepare the patient for a successful discharge.  Yet despite this, heart failure patients 
have the highest readmission rate of any diagnosis.  A growing body of data suggests that untreated sleep 
apnea is a major culprit in this process, with one study showing that the presence of sleep apnea was the 
largest predictor of readmission risk for heart failure patients (Khayat et al. 2012).  Our own preliminary data 
has shown that only 30% of heart failure patients were adherent with their sleep apnea treatment after 
diagnosis, and that non-adherence was associated with increased risk of hospitalization.  We believe 
addressing this problem represents a tremendous opportunity to meaningfully improve patient care. 
Furthermore, the recent introduction of Medicare penalties for readmission, especially heart failure 
readmissions, creates a financial incentive for health care systems to purchase a solution that reduces 
readmissions.  We believe that the AirCare system offers an excellent product-market fit to address this 
challenge.  AirCare will allow sleep apnea patients, for the first time, to receive assistance at night when 
confronted with the myriad of potential challenges that face a PAP user.  The proposed SBIR will extend the 
AirCare platform  to 1) include wireless oximetry, a key outcome measure for effective sleep apnea treatment; 
2) add educational content tailored to sleep apnea and heart failure; 3) create risk classification algorithms that 
will enhance provider efficiency by flagging at-risk patients; 4) integrate with PAP device data to create a 
seamless interface for reviewing symptoms, oximetry and PAP adherence for providers; and 5) conduct a large 
randomized trial to demonstrate effectiveness, a crucial element for a successful commercialization.  
The likelihood of the overall project success is high given the successful track record of AirCare in terms of 
obtaining health system and financial capital endorsement, and the Penn Sleep Center’s history of 
advancement in clinical sleep research.  If the project achieves its aims, we have the opportunity to make a 
meaningful and substantial reduction in hospital readmissions that will both improve the quality of life of the 
more than one million heart failure patients that are admitted each year and reduce health care costs.