Waking people up to sleep Cardiovascular Disease and Sleep-Disordered Breathing Sleep Physician...

Waking people up to sleep

Cardiovascular Disease and Sleep-Disordered Breathing

Sleep PhysicianSleep Physician

ResMed SpecialistResMed Specialist

2 Cardiovascular Disease and Sleep-Disordered Breathing © ResMed 2004

Agenda

• Case study – Heart Block and Sleep Apnea

• Sleep Apnea: Definitions and Prevalence

• Cardiovascular Consequences of Sleep Apnea

• Therapeutic outcomes

• Therapeutic options


Case Study

Case Study: Heart Block Associated Event Associated with OSA

4 Cardiovascular Disease and Sleep-disordered Breathing © ResMed 2003

• 30+ second apnea (no airflow)

• Abdominal effort throughout apnea (obstructive sleep apnea)

• Oxygen saturation drops below 80%

• Heart block event associated with apnea

Case study: ECG Trace and Heart Block Events Associated with OSA


Each episode of heart block is preceded by an apneic event


Sleep Apnea: Definitions and Prevalence


Overview of Sleep Apnea

• Sleep Disordered Breathing (SDB) describes a number of nocturnal breathing disorders

• Sleep Apnea is the dominant type of SDB

– Obstructive sleep apnea (OSA)– Central sleep apnea (CSA)

• OSA and CSA are highly prevalent in patients with cardiovascular disease


Sleep Apnea Types

• Obstructive Sleep Apnea (OSA):– Apnea with ventilatory efforts due to pharyngeal collapse– Patient tries to breathe but can’t due to upper airway obstruction– ~90% of sleep apnea cases1

• Central Sleep Apnea (CSA):– Apnea without ventilatory effort due to withdrawal of central drive– Cheyne-Stokes respiration a subset of CSA– ~10% of sleep apnea cases1

• Mixed Sleep Apnea:– Apnea with central component followed by obstructive component– Often classified as obstructive sleep apnea

1 Young T, Palta M, et al. The Occurrence of Sleep-Disordered Breathing Among Middle-Aged Adults. N Eng J Med; 328: 1230-35.


Sleep Apnea Definitions1

Apnea:Apnea: Cessation of Airflow > 10 sec Cessation of Airflow > 10 sec

Hypopnea:Hypopnea: >50% reduction in airflow for >10 sec>50% reduction in airflow for >10 sec

AHI:AHI: Apnea Hypopnea IndexApnea Hypopnea Index: the number of apneas : the number of apneas and hypopneas per hour of sleepand hypopneas per hour of sleep

Severity Definitions:Severity Definitions:

–Normal: AHI < 5 Normal: AHI < 5 –Mild:Mild: AHI 5 – 14AHI 5 – 14–Moderate: AHI 15 – 30Moderate: AHI 15 – 30–Severe:Severe: AHI >30AHI >30

Sleep Apnea Syndrome:Sleep Apnea Syndrome: AHI of AHI of >> 5 with symptoms. 5 with symptoms.

1 American Academy of Sleep Medicine, Sleep-Related Breathing Disorders in Adults: Recommendations for Syndrome Definition and Measurement Techniques in Clinical Research -AASM Task Force. SLEEP 1999;22(5):667-689.


Prevalence in General Population

• Young et al., NEJM, 1993:328:1230-5– N = 602 (F 250, M 352)– Age 30-60 years, employed

• AHI>5: mild, moderate, or severe sleep apnea*– 24% of middle aged men– 9% of middle aged women– These patients stop breathing >40 times per night

• AHI>15: moderate or severe sleep apnea– 15% of middle-aged men– 5% of middle-aged women– These patients stop breathing >120 times per night


Prevalence of Sleep Apnea increases with age

Young T, et al. Predictors of Sleep-Disordered Breathing in Community-Dwelling Adults. Arch Intern Med 2002; 162: 893-900.


Nasal airflow

Thorax effort

Abdominal effort

SaO2

Snore

Normal Breathing



Obstructive Sleep Apnea

• Most common type of SDB

• Muscles that control the tongue and soft palate relax causing the airway to narrow and close

• Patient tries to breathe but cannot due to airway obstruction

• Patient stops breathing for more than 10 seconds

Obstructive apnea

Normal breathing

ClosedAirway


Obstructive Sleep Apnea (OSA)



Central Sleep Apnea

• Patient makes no effort to breathe in thorax nor abdomen during apnea

• Patient stops breathing for more than 10 seconds

• Typical in severe heart failure patients

• May be characterized by Cheyne-Stokes respiration (CSR) separated by periods of apnea or hypopnea

Normal breathing

Central apnea

OpenAirway


Central Sleep Apnea (CSA)



Cardiovascular Consequences of Sleep Apnea

Increase in blood pressure

Plunging blood oxygen

saturation

Apnea

Surge in sympatheticnerve activity

Negative swingsin intra-thoracic

pressure

Physiological Consequence of Sleep Apnea (Morgan et al. Sleep 1996)

Cardiovascular Disease and Sleep-disordered Breathing


Mechanisms of Sleep Apnea Inducing Cardiovascular Disease

Mechanisms Discussed in Literature:

• Hypoxia resulting directly from apnea

• Negative intra-thoracic pressure from effort to breathe increases cardiac stress

• Pulmonary and systemic hypertension

• Increased sympathetic nerve activity during arousal (neuro-hormonal surge)

• Stimulation of inflammatory pathways

• Endothelial dysfunction


Sleep Apnea and Hypertension

• SDB has a dose-response relationship with hypertension, independent of all known risk factors (age, gender, BMI, smoking, alcohol, others)– Nieto et al. JAMA 2000 (SHHS n=6132) – Lavie et al. BMJ 2000 (n=2677) – Bixler et al. Arch Intern Med 2000 (n=1741) – Peppard et al. NEJM 2000 (WSCS n=709)

Apnea/Hypopnea Index (AHI)

Sleep Apnea and Odd-ration for Developing Hypertension (Lavie et al. BMJ 2000)

Dose-Response relationship between AHI and risk for developing hypertension, independent of confounding factors

21 Cardiovascular Disease and Sleep-disordered Breathing


80%

50%

45%

35%

30%

30%Angina

Coronary ArteryDisease

All Hypertension

Atrial Fibrillation

Congestive HeartFailure

Drug-ResistantHypertension

Sleep Apnea Prevalence in Cardiovascular Disease Patients

Sjostrom et al.Thorax 2002

Logan et al.J. Hypertension 2001

Javaheri et al.Circulation 1999

Schafer et al.Cardiology 1999

Sanner et al.Clin Cardiology 2001

Somers et al.Circulation 2004

v23 Cardiovascular Disease and Sleep-Disordered Breathing © ResMed 2004

Sleep Apnea is an Identifiable Cause of Hypertension

- NIH, JNC7 (2003)


Sleep Apnea and Coronary Artery Disease

• >30% of patients with CAD have sleep apnea

• OSA is an associated with an increased risk of cardiovascular mortality in patients with CAD with a dose-response relationship

Figure 1. By use of a Poisson model the death hazard was calculated as a function of RDI, current age, and time elapsed after the intensive care episode for CAD. The bolded curve gives the function at the current age 70 yr and 3 yr after intensive care. The dotted curves represent 95% CI. Peker Y, Hedner J, Kraiczi H, et al. Am J Respir Crit Care Med. 2000 Vol. 162. Pp 81-86.

AHI


Therapeutic Outcomes


CPAP treats OSA providing a pneumatic splint to keep the upper airway open

Sullivan et al.

Lancet (1981)


OSA: Oxygen Desaturation OSA: Oxygen Desaturation BeforeBefore CPAP CPAP

0102030405060708090

100

0 1 2 3 4 5

Hours

Perc

en

t

O2 Sat

Sullivan, et al., 1981


OSA: Oxygen Desaturation OSA: Oxygen Desaturation AfterAfter CPAP CPAP

0102030405060708090

100

0 1 2 3 4 5

Hours

Perc

en

t

O2 Sat

Sullivan, et al., 1981

A

A = Introduction of CPAP

v

Control Arm

Therapeutic Arm

Effect of nCPAP on Blood Pressure (Becker et al. Circulation 2003)

Average 10 mm Hg reduction in BP predicts:

• Coronary artery disease risk reduced by 37%

• Stroke risk reduced by 56%


60

80

100

120

140

MA

P (

mm

Hg

)

b a se line

e ffe c tive nC P A P

715 pm 1115 pm 315 am 715 am

6 0

8 0

1 0 0

1 2 0

1 4 0

MA

P (

mm

Hg

)

b a se line

sub the ra p e utic nC P A P

7 1 5 pm 11 1 5 pm 3 1 5 am 7 1 5 am

Effect of CPAP on LVEF (Kaneko et al. N Engl J Med 2003)

• Average 35% relative increase in LVEF

• OSA may have an adverse effect in heart failure that can be addressed by CPAP therapy


N=24


Event-free Survival in CAD Patients with OSA: CPAP Therapy and Control Arms

Milleron et al. Eur Heart J 2004;25:728

N=54

n = 64

CPAP Therapy

n = 64

CPAP Therapy

Comparison of Transplant Free Survival in CHF Patients: CPAP vs Control (Sin et al. Circulation 2000)

• 75% five-year survival rate for CHF patients with CSA/CSR on CPAP

• 25% five-year survival rate for CHF patients with CSA/CSR not on CPAP



Therapeutic Options


OSA Therapeutic Methods

• Current:– Nonsurgical treatment:

• Behavior modifications• Nasal Continuous Positive Airway Pressure (CPAP)*• AutoSet CPAP (APAP) devices – increased compliance*

– Surgical treatment:• Uvulopalatopharyngoplasty (UPPP)• Laser-assisted uvulopalatoplasty (LAUP)

• Future:– Adaptive Servo Ventilation

* Discussion focused on CPAP/APAP – Standard of Care


Behavioral Modifications

Methods:

• Weight loss

• Avoidance of alcohol, sedatives, antihistamines, smoking

• Sleeping on side vs. back

Pros:

• Lower risk (vs. surgical/invasive methods)

• Easier to implement and lower cost

• Even a moderate weight loss of 10% corresponds to ~30% decrease in AHI

Cons:

• Requires active patient participation

• Patient compliance low


Positive Airway Pressure

Methods:– Pneumatic stent to keep upper airway open– Continuous positive airway pressure (CPAP): one pressure set – Bi-level (VPAP/BiPAP): two pressures set (inhalation/exhalation)– Auto-CPAP (APAP/AutoSet): device adjusts pressure automatically

Pros:– Non-invasive therapy– Demonstrated to improve AHI, SA symptoms, hypertension, heart

failure status, and other CVD outcomes with effective use– Effective in 80-90% of patients (when used appropriately)

Cons:– Patient compliance is an issue

• Intensive HME support and customization improves compliance• New mask / device technologies improve compliance / efficacy


Patient Using Small, Effective Mask


Autotitration CPAP (APAP or AutoSet)

• AutoSet devices adjust positive airway pressure on a breath-by-breath basis to suit patient needs as they vary throughout the night.

• Acts like a “pacemaker” for sleep apnea with a “preemptive ICD” – algorithm senses and adjusts pressure support as needed to prevent apnea, hypopneas, snore, and flow limitation

• Record patient specific data regarding compliance, device/mask function, and efficacy.


AutoSet for OSA -How it works

• AutoSet Sensors (algorithm triggers)– apneas, – hypopneas, – flow limitation (shape-change of flow-time curve), – snore (flow vibration),– compensation for mask leak

• Ramp pressure to maintain open airway – algorithm approach – preemptive to apnea

• Able to compensate for both intra-night as well as night-to-night variability


AutoSet for OSA – Advantages for Patients

• AutoSet more comfortable than basic CPAP

• Patients report more restful sleep, better quality of sleep, less discomfort from pressure

• Immediate benefits once therapy begins: patients report less trouble getting to sleep

• Varies therapy dose automatically

• Electronic feedback to home medical equipment company – no need for patient diary

• Improves compliance and efficacy


AutoSet for OSA Advantages for Clinicians - 1

• Easier to initiate and titrate – out of the box

• AutoSet has improved patient comfort, compliance, and quality-of-life outcomes (Massie

et al. Am J Crit Care Med v167 pp 20-23 2003)

• Equivalent apnea prevention as CPAP (Lloberes et al. Am J Crit Care Med v154; pp1755-1758 1996)

• Especially useful in patients requiring higher treatment pressures (Randerath et al. Med Sci Monit 2003)


AutoSet for OSA Advantages for Clinicians - 2

• Lower mean pressure overnight– AutoSet mean pressure 37% lower than traditional CPAP– Reduces pressure related side-effects: only uses high pressure

when clinically necessary – No negative effects on sleep architecture or fragmentation

• Automatically adjusts as patient’s needs change both inter-night and intra-night – e.g., weight gain or loss, improving or decompensated

CHF, REM-related apnea, sleeping position, alcohol, etc.

• AutoSet tracks compliance and efficacy– Compliance – hours of use at pressure– Efficacy – Mask Leak, and treatment AHI


Patient Using APAP and Mask


Conclusions on Therapy

• Sleep Apnea is common in patients with cardiovascular disease

• CPAP treatment of sleep apnea is safe and effective

• AutoSet devices (APAP) improve patient comfort, compliance, and quality-of-life outcomes


Therapeutic OutcomesNew Therapies for OSA and CSA


Obstructive Sleep Apnea - OSA (effort to breathe; no flow)

Effort/Abdn

EEG

EOG/LEOG/REMGEKGLAT/RAT

FLOW

Effort/Thorax

SaO2

SNORING

NEED REFERENCES FOR THIS SLIDE


AutoSet Spirit (APAP) for Obstructive Sleep Apnea (OSA)

• Pilot Data of AutoSet on OSA in CHF patients

• After 3 months of AutoSet therapy (n=10)– Apnea-Hypopnea Index – reduced by 90%– BNP – reduced by 45%– 6 minute walk – increased by 20%– LVEF – increased by 5%– Cardiac Output – no significant change

Source: Maisel et al., UCSD, VA Hospital, 2004Source: Maisel et al., UCSD, VA Hospital, 2004


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50

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200

250

300

350

400

450

Baseline 1.5 Months 3 Months 8 Months

Obstructive Sleep Apnea and Congestive Heart Failure

Case Study: 69 year-old, male

BNP

(pg/mL)

AutoSet downloadMask Leak noted

AutoSet downloadCompliance > 4 hrs/nightAHI<5 events/hour

AHI = 26 events per hourNadir O2 was 81%


Leak eliminatedC>4h/n AHI<5


0

500

1000

1500

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Baseline 3 Months 8 Months

Obstructive Sleep Apnea and Congestive Heart Failure

Case Study: 69 year-old, male

6 m

in. w

alk

(fe

et)

AHI = 26 per hourNadir O2 = 81%

AutoSet downloadMask Leak noted

Leak eliminatedC>4h/n AHI<5

Up 35%



Conclusions

• AutoSet devices are easier to initiate, adjust to changes over time, and provide feedback

• AutoSet devices may increase the number of patients successfully treated for Sleep Apnea leading to improved cardiovascular outcomes

• Summary of key cardiovascular outcomes improved with positive airway pressure:– Blood Pressure– Ejection Fraction– Quality of Life– Survival Rate


Central Sleep Apnea - CSA (no effort to breathe; no flow)

Effort/Abdn

EOG/L

EOG/R

EMG

EKG

LAT/RAT

FLOW

Effort/Thorax

SaO2

EEG


Adaptive Servo Ventilation for Central Sleep Apnea (CSA)

• Pressure Support Adaptive Servo Ventilator

• Design Goals:– Direct suppression of CSA/CSR– More comfortable than traditional CPAP– Easier to introduce than CPAP & bi-level– Similar hemodynamic/cardiovascular benefits

• Called AutoSet CS*– Central Sleep Apnea– Cheyne-Stokes Respiration

* Informational purposes onlyCurrently in FDA trialNot available for sale in the U.S.



Mechanism of Action:

• Supplements ventilation during apneic and hypopneic phases of breathing cycle

• Reduces support during hypercapneic phase to avoid hyperventilation

• Target overall minute ventilation of 90% of the ventilation of the past 300 seconds



• Patients with central sleep apnea treated with oxygen, CPAP, bi-level, and Adaptive Servo Ventilator (AutoSet CS*)

• N = 14 patients in Acute Setting

(Teschler H, et al., Am J Respir Crit Care Med 164: 614-19, 2001)



N=14



Adaptive Servo VentilationEssen Long-term Study

• N=20 Patients in Chronic Setting (Home Study)– N=10 patients– N=10 placebo controls

• 6 months home therapy on AutoSet CS*

• Assess cardiac, respiratory, and QOL data

• N=12 completed and available



Pilot Data: Essen Long-term StudyAdaptive Servo-Ventilation

Compliance 6.3 hr/night for 6 months

Key Outcomes:

• 27% improvement in VO2 max

• 35% improvement in 6 minute walk

• 38% improvement in MLHFQ

• 55% reduction in nocturia episodes

• 88% reduction in AHI N=12



Adaptive Servo-Ventilation and CSA/CSR

AutoSet CS* [on]

Airflow Measurement

Pressure from AutoSet CS

Blood Oxygen Level (SaO2%)

AutoSet CS* [off]



Conclusions

• Adaptive Servo Ventilation suppresses CSA and CSR

• Adaptive Servo Ventilation is more effective than:– Oxygen– CPAP– Bi-level

• Summary of key cardiovascular outcomes improved with adaptive servo ventilation:– VO2 max– Six minute walk– Minnesotta Living with Heart Failure Questionnaire

• AutoSet CS is currently in FDA trials

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