Sleep Apnea Treatment

William T. Abraham, MD, FACP, FACC, FAHA, FESCProfessor of Medicine, Physiology, and Cell BiologyChair of Excellence in Cardiovascular MedicineDirector, Division of Cardiovascular MedicineAssociate Dean for Clinical ResearchDirector, Clinical Trials Management OfficeDeputy Director, Davis Heart & Lung Research Institute

The Ohio State UniversityDivision of Cardiovascular Medicine

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§ CPAP § Surgical therapies (e.g., uvuloplasty)§ Dental implants§ Implantable devices

Therapies for Obstructive Sleep Apnea

CPAP Therapy

Compliance with CPAP is an Issue in OSA Patients

Schoch et al. Respiration 2014

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CPAP Lowers Blood Pressure in OSA Patients

Becker et al. Circulation 2003

CPAP Improves survival in OSA Patients After Stroke

§ Randomized controlled trial in post-stroke patients

§ Significant decrease in all-cause mortality and in cardiovascular events in the group which used CPAP

Parra et al. J Sleep Res 2015

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CPAP Improves LV Function in HF Patients with OSA

Kaneko et al, NEJM 2003

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5

10

15

20

25

30

35

40

Control ControlCPAP CPAP

LVEF, % FS, %

Baseline

1 mo

nsp=0.002

ns

p<0.001

p=0.009

p=0.044

§ Non-randomized study comparing treated versus non-compliant patients

CPAP Improves Event Free Survival in HF Patients with OSA

Kasai et al. Chest 2008

Multiple Surgical Techniques Available for OSA

§ Surgical options depend on the individual patient anatomy

§ Overall success is about 50%

§ Tracheostomy is considered a “cure” for OSA

§ Unclear if these procedures can work in the setting of fluid shifts seen in HF

Multiple Surgical Options for OSA

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Dental Appliances for OSA

Hypoglossal Nerve Stimulation Device

§ Currently available device is surgically implanted with two leads that causes tongue protrusion by stimulation of the hypoglossal nerve via a cuff electrode that opens the palate to decrease obstructive sleep apnea

§ Screened patients who did not tolerate or accept CPAP

§ Requires endoscopy while sleeping to determine if patient had complete airway collapse

Inspire Medical Systems, Maple Grove, Minnesota, USA

Primary outcomes:

§ Significant change in AHI at 12 months compared to baseline (32 to 15 events/hour) (p<0.001)

§ Significant change in ODI at 12 months compared to baseline (29 to 14 events/hour) (p<0.001)

§ 66% responders by AHI (50% reduction in AHI and AHI < 20 events/hour)

§ 75% responders by ODI (25% reduction; events/hour)

Results of the Hypoglossal Nerve Stimulation Device Trial

Strollo et al. NEJM 2014

§ Oxygen§ Symptomatic relief only§ No long term efficacy seen to date

§ Medications§ Only small, short term studies§ Acetazolamide, theophylline§ Static or intermittent carbon dioxide

CSA Treatments Have Not Demonstrated Long-Term Benefit

§ Positive Airway Pressure Therapies§ CPAP/BiPAP

§ Poor compliance and patient acceptance § Delivers positive pressure into the lungs which increases

pressure to the right side of the heart§ Improved EF and QOL§ Questionable long term benefit (CANPAP showed

decreased mortality only in compliant patients who also showed AHI reduction)

§ ASV§ SERVE-HF demonstrated increased cardiovascular mortality

using ResMed System§ Only very early SERVE-HF data is currently available§ No multi-center, randomized, controlled trial with surrogate

endpoints prior to SERVE-HF

CSA Treatments Have Not Demonstrated Long-Term Benefit

§ Did patients wear the device?

§ Was AHI effectively lowered?

§ Could positive pressure devices cause harm?

§ Could patients with very low EF be too ill for the therapy?

Why Would Positive Airway Pressure Therapy Fail to Improve Cardiovascular Mortality in HF Patients with CSA?

Comparison of Normal Inspiration with Mask-Based Therapies

Normal Breathing

Mask Therapies (ASV, CPAP)

Diaphragm pulls air into the lungs via negative intrathoracic pressure

Ventilation pushes air into the lungs via positive pressure (intrathoracic pressure less negative)

§ Normal inspiration§ Small increases in afterload§ Small increases in LVEDV§ Increased RV filling§ Decreased RV afterload

§ Heart rate decreases

§ Maintains cardiac output

§ Positive airway pressure ventilation§ Large decreases in afterload§ No change in LVEDV§ Decreased RV filling§ Increased RV afterload

§ No change in heart rate

§ Could cause decrease in cardiac output if volume normal-low (Frank Starling mechanism)

Physiologic Changes with Normal Inspiration Compared to Positive Airway Pressure

§ OSA has multiple treatment options§ CPAP§ Demonstrated improved mortality in the non-HF population§ Early data suggest improved mortality in the HF population

§ Surgical approaches have not been studied in HF population§ Limited data in HF with dental appliances and hypoglossal nerve

stimulation

§ CSA has had limited treatment options§ Oxygen has not shown long-term benefit§ Medications have only shown short term improvements§ Positive airway pressure therapies do not appear to be optimal

long term therapeutic approaches

§ Innovative therapeutic approaches are needed for CSA

Conclusions