Upper Airway Pacing for Obstructive Sleep Apnea Charles W. Atwood, Jr., MD, FCCP, FAASM Assoc Professor of Medicine University of Pittsburgh Sleep Program Director, VA Pittsburgh Healthcare System
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Upper Airway Pacing for Obstructive Sleep Apnea Charles W. Atwood, Jr., MD, FCCP, FAASM Assoc Professor of Medicine University of Pittsburgh Sleep Program.
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Slide 1
Upper Airway Pacing for Obstructive Sleep Apnea Charles W.
Atwood, Jr., MD, FCCP, FAASM Assoc Professor of Medicine University
of Pittsburgh Sleep Program Director, VA Pittsburgh Healthcare
System
Slide 2
Disclosure: Charles W. Atwood, Jr., MD Research Support Federal
NIH, NIDDK - OSA Dept of Defense Lung cancer Industry Research
Grant Philips-Respironics, Inc. Forest Research Institute Industry
advisory -Philips-Respironics -Carecore National
Slide 3
Outline Background Upper Airway Stimulation STAR Trial
Conclusions
Slide 4
Pathogenesis of Obstructive Sleep Apnea AJRCCM 2005
172:13631370 Promotion of Airway Collapse Promotion of Airway
Patency Negative pressure on inspiration Extralumenal positive
Pressure Fat Deposition Small mandible Pharyngeal dilator Muscle
contraction (genioglossus) Lung volume (longitudinal traction) Risk
Mediated by a: Gene (Obesity, Craniofacial Structure, Respiratory
Control / Environment (Obesity) Interaction
Slide 5
Sleep 2008 31:1071-78 Sleep Disordered Breathing and Mortality:
Eighteen-Year Follow-up of the Wisconsin Sleep Cohort (n = 1396)
SDB, irrespective of EDS, was associated with increased mortality.
The striking high CV mortality risk in untreated severe SDB,
suggests that SDB Rx should not be contingent on daytime sleepiness
symptoms
Slide 6
Increased Prevalence of Sleep-Disordered Breathing in Adults
The current prevalence estimates of moderate to severe
sleep-disordered breathing (apnea-hypopnea index, measured as
events/hour, 15) are: 10% (95% CI: 7, 12) among 3049-year-old men
17% (95% CI: 15, 21) among 5070-year-old men 3% (95% CI: 2, 4)
among 3049-year-old women 9% (95% CI: 7, 11) among 5070 year-old
women These estimated prevalence rates represent substantial
increases over the last 2 decades - relative increases of between
14% and 55% depending on the subgroup Am J Epidemiol.
2013;177(9):10061014
Slide 7
OSA and Cardiovascular Disease Primary HTN: 35% prevalence
Drug-resistant HTN: 65 to 80% prevalence Most common secondary
cause Coronary Artery Disease: 30% prevalence Heart failure: 21-37%
prevalence Atrial Fibrillation: OSA present 5 X more likely Stroke:
60% prevalence Circulation 2012;126:1495-1510
Slide 8
Cumulative Incidence of Fatal CV Events Cumulative Incidence of
Non-fatal CV Events AIM: Observational study to compare incidence
of fatal and non-fatal cardiovascular events in simple snorers,
patients with untreated OSA, patients treated with CPAP, and
healthy men recruited from the general population. Design:
Prospective observational cohort. 264 healthy men, 377 simple
snorers, 403 with untreated mild-moderate OSA (AHI 5-30), 235 with
untreated severe OSA (AHI > 30), and 372 with OSA and treated
with CPAP Lancet 2005 365: 104653 Months. Conclusion: In men,
severe OSA significantly increases the risk of fatal and non-fatal
cardiovascular events. CPAP treatment reduces this risk. Long-term
cardiovascular outcomes in men with OSA
Slide 9
CPAP Therapy and Adherence PAP therapy when used consistently
results in decreased daytime sleepiness*, improved HRQOL, and
decreased vascular risk. Recent studies of CPAP therapy
investigated adherence: APPLES Study largest RCT in sleep medicine
to date (1,516 subjects enrolled) and CPAP adherence rate was 39%
at 6-months use of CPAP therapy (174 of 443) Home PAP Study
Evaluation of standard OSA care vs. home-base diagnostics and
titration. Results of 3-month follow-up: CPAP adherence was 39%
(Lab titration); CPAP adherence was 50% (Home titration)
Conclusion: CPAP is first-line therapy and effective when
consistently used by OSA patients. Alternative therapy options for
moderate or severe OSA patients who are nonadherent to PAP are
desirable
Slide 10
OSA Value of Selected Treatment Options SnoringMild Sleep Apnea
Moderate or Severe Sleep Apnea Weight loss Nasal decongestant
Positional therapy Surgery (adults) Surgery (children) Oral
appliance PAP Darker more valuable. Upper Airway Stimulation
therapy treatment indication Only Positive Airway Pressure (PAP)
and Surgery indicated for patients with Moderate or Severe OSA
http://www.sleepapnea.org/diagnosis-and-
treatment/treatment-options.html
Slide 11
Outline Background Upper Airway Stimulation STAR Trial
Conclusions
Slide 12
The Inspire System: Built on a proven, commercial grade
technology platform Stimulation Lead - Self sizing cuff - Multiple
stimulation vectors Implanted Pulse Generator (IPG) - 6-8 year
projected longevity Effort Sensor - Secure, stable location -
Direct measurement of ventilatory effort - Short surgical
tunnel
Slide 13
Upper Airway Anatomy & Stimulation Site Stimulation Site:
Medial branch of the hypoglossal nerve, activates only protrusors
(genioglossus, geniohyoid), distal to retractors (styloglossus and
hyoglossus) Styloglossus (SG) Hypoglossal Nerve (XII) Hyoglossus
(HG) Superior root of ansa cervicalis Genioglossus (GG) Geniohyoid
(GH) Thyrohyoid Stimulation Site Superior Longitudinal Inferior
Longitudinal
Slide 14
No airway anatomy alteration Works with patients physiology
Standardized implant technique Fast post op recovery Patient
Programmer Turn therapy ON/OFF Adjust amplitude Device Programmer
Adjust Therapy Parameters Bluetooth enables remote adjustments
during titration studies in the sleep lab Upper Airway
Stimulation
Upper Airway Stimulation advances tongue to open airway Airway
Obstructed STIMULATION OFF Tongue Advanced STIMULATION ON Tongue
base Epiglottis Tongue base advancement with stimulation Tongue
base Observed during sleep endoscopy
Slide 17
Effect of stimulation on the Retropalatal and Retrolingual
airway area between awake endoscopy and DISE Eur Respir J 2014; in
press
Slide 18
Increases in retropalatal and retrolingual area comparing no
stimulation with progressively higher levels of stimulation during
DISE No stimulation First sensationBulk movementTitrated
therapeutic Sub-discomfort Retropalatal Retrolingual Eur Respir J
2014; in press
Slide 19
PSG: Effect of Stimulation Therapy ONTherapy OFF 30 seconds EEG
EMG Nasal Pressure Thermo Chest Abdomen SpO2
Slide 20
In-lab PSG Titration Algorithm Increase amplitude by 0.1 to 0.2
volts if 5 obstructive apneas or hypopneas or loud, unambiguous
snoring 10 min Start: 0.2 V below Functional Threshold Reduce
amplitude by 0.1 to 0.2 volts if stimulation causes persistent
arousals or is poorly tolerated Amplitude (volts) Time (minutes)
Therapeutic Amplitude Range 30 minutes in the patients preferred
sleep position with minimum occurrence of events, preferably with
REM sleep observed Arousal Threshold 20 *Adapted from current
practice guidelines established for CPAP titration by the American
Academy of Sleep Medicine, ref: Journal of Clinical Sleep Medicine,
Vol. 4, No 2, 2008
Slide 21
Clinical Trial Experience Proof of Principle Trial 8 patients 4
Centers Completed in 2001 Demonstrated therapy concept Feasibility
Trial 34 patients 8 Centers Completed in 2010 Demonstrated safety
and patient selection References: 1.Operative technique in
otolaryngology-head and neck surgery. 2012 23(3): 227-33 2.Journal
of Clinical Sleep Medicine 2013 9 (5) 433-438 3.The Laryngoscope
2012 122(7): 1626- 33 Reference: Arch Otolaryngol Head Neck Surg
2001 127:1216-1223
Slide 22
Examples collapse at the level of the palate during DISE
Anteroposterior collapse Concentric collapse JCSM 2013 9 (5)
433-438
Slide 23
Inspire UAS effect during DISE Palate Therapy OFF Palate
Therapy ON Posterior oropharyngeal wall Posterior Uvula LR P
Epiglottis Lingual Tonsils LR P L R P L R P Reference: 2 slices
Palate Tongue-Base Tongue B ase Therapy OFF Tongue Base Therapy
ON
Slide 24
Outline Background Upper Airway Stimulation STAR Trial
Conclusions
Slide 25
Stimulation Therapy for Apnea Reduction (STAR Trial)
ClinicalTrials.gov NCT01161420 Hypothesis: Unilateral Stimulation
of the Hypoglossal Nerve during sleep will safely and effectively
treat Obstructive Sleep Apnea NEJM 2014 370:139-49
Slide 26
Outcome Measures: Baseline vs. 12-Months Co-Primary Apnea
Hypopnea Index Oxygen desaturation index (ODI 4% ) Secondary
Epworth Sleepiness Scale Functional Outcomes of Sleep Questionnaire
SaO2 < 90% NEJM 2014 370:139-49
Slide 27
Methods I Prospective, multicenter trial with randomized
therapy withdrawal arm in participants with moderate to severe OSA
who had failed or had not tolerated CPAP. All underwent a screening
polysomnographic (PSG) study, surgical consultation, and drug-
induced sedation endoscopy (DISE). Participants without complete
concentric collapse at the retropalatal airway received an
implanted neurostimulator NEJM 2014 370:139-49
Slide 28
Inclusion Criteria AHI between 20 and 50 Have failed or have
not tolerated CPAP Central and mixed sleep apnea accounted for <
25% of all AHI events Absence of significant apnea when sleeping in
a non-supine position (AHI non-supine > 10) 28 NEJM 2014
370:139-49
Slide 29
Exclusion Criteria BMI > 32 Neuromuscular diseases Severe
Co-Morbid Cardiopulmonary Disease Other chronic sleep disorders
Complete concentric collapse at the level of soft palate during
drug-induced sedation endoscopy (DISE) 29 NEJM 2014 370:139-49
Slide 30
Examples collapse at the level of the palate during DISE
Anteroposterior collapse Concentric collapse JCSM 2013 9 (5)
433-438
Slide 31
Methods II Participants were followed for 12 months to assess
efficacy and adverse events. PSG (AHI and ODI) Quality of life
measures Epworth Sleepiness Scale (ESS) Functional Outcomes of
Sleep Questionnaire (FOSQ) Responders after 12 months of continuous
therapy were randomized to one week of therapy suspension (OFF) vs.
therapy maintenance (ON) and evaluated with PSG. NEJM 2014
370:139-49
Slide 32
Consort Flow Chart NEJM 2014 370:139-49
Slide 33
Baseline Characteristics of the Study Population (N = 126)
CharacteristicsMean SD or N (%) Age, year54.5 10.2 Male sex, no.
(%)83% Caucasian race, no. (%)97% Body Mass Index, kg/m 2 28.4 2.6
Neck size, cm41.2 3.2 Systolic BP, mmHg128.7 16.1 Diastolic BP,
mmHg81.5 9.7 Hypertension, no. (%)38% Diabetes9% Asthma5%
Congestive heart failure2% Prior UPPP, no. (%)18% NEJM 2014
370:139-49
Slide 34
Primary Outcome Measures: AHI and ODI (n = 124) 68% reduction
in AHI from baseline to Month-12 70% reduction in ODI from baseline
to Month-12 AHIODI *Median and error bar in standard error p <
0.0001 NEJM 2014 370:139-49
Slide 35
Secondary Outcome Measures: FOSQ & ESS (n = 123) FOSQ
ScoreESS Scale *Median and error bar in standard error p <
0.0001 NEJM 2014 370:139-49
Randomized Controlled Therapy Withdrawal *mean and error bar in
standard error p < 0.0001 p = n.s. NEJM 2014 370:139-49
Slide 38
Relevant Adverse Events Serious: Device related 1% Device
revision Non Serious: Procedure related ~ 25% Pain (minimal, most
did not require narcotics - substantially less than UPPP)
Non-Serious: Device related ~ 33% Tongue discomfort / abrasion
(time limited) 1% Mild or Mod Infection (cellulitis) * One Death
Unrelated to the Trial NEJM 2014 370:139-49
Slide 39
Adherence Data After 12 months follow up of 126 implanted
participants, 124 participants (98%) remained active users of UAS
therapy. One participant died unexpectedly due to an unrelated
cause, and one participant requested a device removal for personal
reasons. Based on self reports from 123 participants at 12 months,
86% (106 of 123) used the device daily and 93% (115 of 123) used
the device at least 5 days a week. The UAS device registers the
cumulative hours of stimulating pulses duration since last device
interrogation. At the 12-month visit, the average stimulation
pulses time was 2.6 hours per night. The stimulating pulses were
not delivered continuously during sleep, and were only delivered
during the late expiratory and inspiratory phases of respiration.
NEJM 2014 370:139-49
Slide 40
Measurement of Use of Therapy NEJM 2014 370:139-49
Slide 41
Upper Airway Stimulation effect on Sleep Baseline N = 126 12
Month N = 124 Sleep Time, min Mean(SD) % of Total Sleep Mean(SD) %
of Total Sleep P value Total Sleep 364.8 (68.0) 333.7 (69.3)