The Role of Sleep Disordered Breathing in Heart Failure Admissions

The purpose of this study is to evaluate the effect of in-hospital diagnosis and treatment of
sleep disordered breathing (SDB) on post-discharge mortality and readmissions in-
hospitalized patients with heart failure and reduced ejection fraction (HFrEF). The study is
a randomized controlled trial in HFrEF patients who are hospitalized with acute heart failure
syndrome (AHFS) and have an in-hospital sleep study diagnostic of SDB. Participants will be
randomized to either the current standard of care of AHFS treatment or an intervention arm in
which expedited treatment with adaptive servo ventilation is initiated immediately upon
in-hospital diagnosis of SDB.

Inclusion Criteria:

1. Admission diagnosis of heart failure and AHFS as defined by the following: A chief
complaint of dyspnea or fatigue; elevated left ventricular pressure. Elevated left
ventricular pressure is indicated by at least one of the following: signs of volume
overload pedal edema, crackles, consistent chest X-ray, increased measurement of left
ventricular end-diastolic diameter or volume, or elevated BNP level.

2. Previously unrecognized or recognized but untreated SDB diagnosed or confirmed on
attended inpatient sleep study during the index hospitalization with AHFS. SDB is
defined as one of the following syndromes:

1. AHI>15 with more than 50% apneas being central (CSA); or

2. AHI>30 events with more than 50% of the events being obstructive (severe OSA) in
patients with LVEF <30%.

3. Projected length of stay >2 days on admission day to ensure uniformity of the
underlying severity of the AHFS and to enable the introduction of the ASV device and
education

4. LVEF <45% within 1 year of admission. An echocardiogram may be performed to confirm
the LVEF during the hospitalization to determine eligibility.

5. Ongoing targeted treatment for heart failure during the current hospitalization
including at least one of the following: IV diuretics, IV infusion of inotropes or
vasodilators, or planned revascularization, or device therapy.

Exclusion criteria:

1. Patients who were on supplemental oxygen for an indication other than SDB or heart
failure prior to admission. These are patients who have chronic respiratory
insufficiency.

2. Patients on treatment targeting CSA or OSA (ASV, oxygen, or CPAP); and patients who
already provided and rejected positive airway pressure therapy due to intolerance of
the pressure or the claustrophobia.

3. Cardiogenic shock and hemodynamic instability with MAP less than 55 mmHg off
vasopressors, or concurrently on vasopressor treatment, left ventricular assist
devices, or intra-aortic Balloon Pump. Inotropic agents will not constitute an
exclusion criterion. Patients will be eligible once more stable off vasopressors.

4. Acute respiratory failure or insufficiency defined by (PaO2/FIO2) ratio less than 250,
or FIO2 requirement more than 40%. Patients are eligible to participate once their
FIO2 requirement is below 30%.

5. Overt neurological deficit or patients who arrived from a long-term care facility or
expected to be discharged to one; and patients who have very poor functional outcome
precluding ability to use the ASV device independently

6. Renal failure requiring renal replacement therapy; Patients will not be excluded if
they were undergoing ultra-filtration for volume removal.

7. Moderate to severe chronic obstructive lung disease (FEV1/FVC < 55%).

8. Patients who are likely to receive heart transplant or left ventricular assist device
(LVAD) in the subsequent year. These are patients who have high standing on the
transplant list during the index hospitalization or have a cardiothoracic evaluation
for implantation of LVAD.

9. Patients on long term or "bridging" inotropic infusion, or short life expectancy due
to concomitant illness or heart failure

10. Patients who report severe sleepiness or who consider themselves at risk while
driving.

11. Patients who fail the secondary screening procedure. Secondary screening procedure
involves the patient being asked to wear the device and experience the pressure
delivery for at least 30 minutes while relaxed.