Sleep Apnea: Sleep Apnea:

……the heart suffers even in our sleep...the heart suffers even in our sleep...

Adrián BaranchukAdrián BaranchukAssociate Professor of Medicine and PhysiologyAssociate Professor of Medicine and Physiology

Queen’s UniversityQueen’s UniversityKingston, Ontario, CanadaKingston, Ontario, Canada

Cosme Argerich Hospital SymposiumCosme Argerich Hospital SymposiumOctober 2010October 2010

Sleep Apnea and Cardiovascular DiseaseSleep Apnea and Cardiovascular Disease

1.1. Definitions and clinical symptoms Definitions and clinical symptoms

2.2. Epidemiology Epidemiology

3.3. Pathophysiology Pathophysiology

4.4. The link between SA and the cardiovascular systemThe link between SA and the cardiovascular system

5.5. Methods of studyMethods of study

6.6. Brief summary of managementBrief summary of management

7.7. Areas of investigationAreas of investigation

DefinitionsDefinitions

1.1. SA:SA: presence of apneas and hypopneas during sleep, symptomatic by abrupt presence of apneas and hypopneas during sleep, symptomatic by abrupt

awakening (arousals), snorting and daily sleepinessawakening (arousals), snorting and daily sleepiness

2. 2. Apnea:Apnea: interruption of aerial flow, with saturation reduction of 0 interruption of aerial flow, with saturation reduction of 022 ≥ 4% ≥ 4%

► ► CentralCentral: impairment of nervous centers that regulate breathing: impairment of nervous centers that regulate breathing

► ► ObstructiveObstructive: reduction of aerial flow in the upper respiratory airway: reduction of aerial flow in the upper respiratory airway

3. 3. Hypopnea:Hypopnea: decrease of ≥30% of aerial flow or thoracoabdominal excursion, decrease of ≥30% of aerial flow or thoracoabdominal excursion,

with saturation reduction of 0with saturation reduction of 02 2 ≥ 4%≥ 4%

4. 4. AHI (Apnea/hypopnea index):AHI (Apnea/hypopnea index): number of apneas and hypopneas per number of apneas and hypopneas per

hourhour

Sleep ApneaSleep Apnea

Sleep Apnea:Sleep Apnea:PathophysiologyPathophysiology

Mechanisms of obstruction of airways during sleep:Mechanisms of obstruction of airways during sleep:

1.1. Subatmospheric intraluminal pressureSubatmospheric intraluminal pressure

2.2. Expiratory narrowingExpiratory narrowing

3.3. Ventilatory-motor reductionVentilatory-motor reduction

4.4. Mixed theory: central + obstructiveMixed theory: central + obstructive

The link between SA and cardiovascular morbidityThe link between SA and cardiovascular morbidity

1.1. Physiologic changes during sleepPhysiologic changes during sleepa.a. In NREM stage: BP and HR drop (10-20%): ↓ of MV and TPR, In NREM stage: BP and HR drop (10-20%): ↓ of MV and TPR,

↓ ↓ sympathetic tone in phase 4 of NREMsympathetic tone in phase 4 of NREMb. In REM stage: vasoconstriction + fluctuation of MV and HR b. In REM stage: vasoconstriction + fluctuation of MV and HR

2.2. Acute changes during SAAcute changes during SA

a.a. HR:HR: there are 2 patterns of behavior there are 2 patterns of behavior- Bradycardia at the onset of apnea, acceleration during SA - Bradycardia at the onset of apnea, acceleration during SA (chemoreceptors) and acceleration peak at the end of apnea (chemoreceptors) and acceleration peak at the end of apnea and when awakening and when awakening (more frequent)(more frequent)-- Progressive bradycardia along the apnea

b. BP: increase at the end of apnea (> desaturation, ↑ , ↑ sympathetic tone by sudden awakening)sympathetic tone by sudden awakening)

c.c. Minute volume:Minute volume: ↓ ejection volume during apnea ↓ ejection volume during apnea accompanied by intrapleural negative pressureaccompanied by intrapleural negative pressure

Pathophysiologic mechanisms Pathophysiologic mechanisms of cardiovascular morbidityof cardiovascular morbidity

Sleep Apnea

In summary…In summary…

SASA

Fluctuations of BP, HR and minute volume + Desaturation 02

Cardiovascular morbidityCardiovascular morbidity

Acute changes Chronic changes

•Arrhythmias •Myocardial infarction•Stroke

•CHF •HTN•Pulmonary HTN•LVH

1.1. BradyarrhythmiasBradyarrhythmias

- Sinus arrest- Sinus arrest

- AV block- AV block

2.2. TachyarrhythmiasTachyarrhythmias

- Atrial fibrillation- Atrial fibrillation

- Ventricular arrhythmias- Ventricular arrhythmias

Sleep Apnea:Sleep Apnea:SA and ArrhythmiasSA and Arrhythmias

What has been proven from all of this?What has been proven from all of this?

Sleep Apnea:Sleep Apnea:SA and ArrhythmiasSA and Arrhythmias

The association between SA The association between SA and AF is highly significant. and AF is highly significant. SA is also associated to SA is also associated to ventricular arrhythmias.ventricular arrhythmias.

Sleep Apnea:Sleep Apnea:SA and AFSA and AF

Sleep Apnea

Tachyarrhythmias Bradyarrhythmias

Atrial overdrivepacing

Heart failure

• Supra/ventricular arrhythmia• ? CRT

Autonomic dysfunction

• Atrial Fibrillation• Ventricular arrhythmia

• Systemic hypertension• Pulmonary hypertension

Stroke

Baranchuk et al. Europace 2008; 10(6):666-667 Baranchuk et al. Europace 2008; 10(6):666-667

Sleep Apnea :Sleep Apnea :SA and ArrhythmiasSA and Arrhythmias

Baranchuk et al. Europace 2008; 10(6):666-667 Baranchuk et al. Europace 2008; 10(6):666-667

AF + SA

HypertensionHypertension

Autonomic ImbalanceAutonomic Imbalance

Bi-atrial enlargement*Bi-atrial enlargement*

Heart failureHeart failure

? CAD? CADInteratrial block*Interatrial block*

Baranchuk A et al. Rev Electrofisol y Arrit 2008;1:5-6Baranchuk A et al. Rev Electrofisol y Arrit 2008;1:5-6 *Interatrial Block in Patients with OSA*Interatrial Block in Patients with OSABaranchuk et al Cardiol J;2010,in Press)Baranchuk et al Cardiol J;2010,in Press)

Sleep Apnea:Sleep Apnea:SA and ArrhythmiasSA and Arrhythmias

Zwillich C. J Clin Invest 1982;69:1286-92Zwillich C. J Clin Invest 1982;69:1286-92

• Bradycardia during SA•The greater the apnea, the greater the bradycardia•No bradycardia in absence of SA

Baranchuk et al. Case Reports Med 2009Baranchuk et al. Case Reports Med 2009

ECG recording of polysomnography is

a single lead and at times, it may be

confusing. In this case, the patient was

referred due to 2:1 block and in fact,

these are premature contractions

of the RV outflow tract.

Sleep Apnea:Sleep Apnea:Management with PacemakerManagement with Pacemaker

Sequential pacemaking did not show benefits in patients with SA

JACC 2006;47:379-83JACC 2006;47:379-83

Atrial overdrive pacing: 12 RCT since 2002…Atrial overdrive pacing: 12 RCT since 2002…

• The benefits are not clear…The benefits are not clear…

Baranchuk et al. Europace 2009. Baranchuk et al. Europace 2009.

Reduction of AHI in 5 points:Reduction of AHI in 5 points:Statistically significant but…Statistically significant but…No clinical relevance!!!No clinical relevance!!!

Baranchuk et al. ICRJ 2008;2(1):10-13Baranchuk et al. ICRJ 2008;2(1):10-13

Sleep Apnea:Sleep Apnea:Coronary Artery DiseaseCoronary Artery Disease

Eur Respir J 2006;28:596-602

(n=308)(n=308)Follow up: 7 yearsFollow up: 7 yearsSA: AHI ≥ 30SA: AHI ≥ 30

BASAL

With SAw/o SA

Sleep Apnea:Sleep Apnea:Coronary Artery DiseaseCoronary Artery Disease

(n=6424)(n=6424)AHI divided into quartilesAHI divided into quartilesMultivariate analysis and adjusted by co-variablesMultivariate analysis and adjusted by co-variables

Related mechanismsRelated mechanisms

1.1. HypertensionHypertension

2.2. Daytime sympathetic hyperactivityDaytime sympathetic hyperactivity

3.3. HypoxemiaHypoxemia

4.4. ↑ ↑ platelet aggregationplatelet aggregation

5.5. Acute rupture of plaqueAcute rupture of plaque

6.6. Pulmonary hypertensionPulmonary hypertension

Sleep Apnea :Sleep Apnea :Coronary Artery DiseaseCoronary Artery Disease

Milleron O. Eur H Journal 2004;25:728-734Milleron O. Eur H Journal 2004;25:728-734

• (n=54)• Patients on SA + CAD• CPAP/ surgery vs no treatment• Composite end-point: cardiovascular mortality, ischemic event, hospitalization by CHF, revascularization

Treatment No treatment6/25 (24%) 17/29 (58%)HR 0.24 (95% CI 0.09 – 0.62)

P<0.01

Who is worried about this…?Who is worried about this…?

AUGUST 2008 (On-LINE)AUGUST 2008 (On-LINE)

Sleep Apnea:Sleep Apnea:StrokeStroke

Investigating the Relationship Between Stroke and Obstructive Sleep Apnea

Dyken ME. Stroke 1996;27:401-407Dyken ME. Stroke 1996;27:401-407

SASA

strokestroke

strokestroke

SASA?

Should we rewrite theShould we rewrite theCHADS2 score?CHADS2 score?

SA & Heart FailureSA & Heart FailureMechanism of interactionMechanism of interaction

SA & Heart FailureSA & Heart FailureClinical scenariosClinical scenarios

1. Left ventricular dysfunction1. Left ventricular dysfunction

(n=47)(n=47)EF < 40%EF < 40%AHI > 15AHI > 15

ResultsResults

1. SA: 55% of pts1. SA: 55% of pts2. More frequent in CAD2. More frequent in CAD

Circulation 2003,197:727-732Circulation 2003,197:727-732

2. Congestive heart failure2. Congestive heart failure

(n=450)(n=450)EF 27.3EF 27.315%15%NYHA II: 62%, NYHA III: 34%NYHA II: 62%, NYHA III: 34%AF: 15%AF: 15%AHI > 20AHI > 20

ResultsResults

1.1. SA (AHI>20): 53%SA (AHI>20): 53%2.2. More frequent in AF (p<0.01)More frequent in AF (p<0.01)

Am J Respir Crit Care Med 1999,160:1101-06Am J Respir Crit Care Med 1999,160:1101-06

SA & Heart FailureSA & Heart FailureClinical scenariosClinical scenarios

3. Diastolic dysfunction3. Diastolic dysfunction

(n=20)(n=20)NYHA II-IIINYHA II-IIIAHI > 10AHI > 10

ResultsResults

1.1. SA (AHI>10): 55%SA (AHI>10): 55%2.2. Time of decelerationTime of deceleration

(p<0.05)(p<0.05)

Chest 1997,111:1488-93Chest 1997,111:1488-93

SA & Heart FailureSA & Heart FailureClinical scenariosClinical scenarios

(n=24)(n=24)

Non-randomized studyNon-randomized study

Ambulatory polygraphAmbulatory polygraph

1. Significant reduction of AHI (pre CRT vs post CRT)2. Significant increment of SaO2 3. Significant reduction of PSQI (Pittsburgh Sleep Quality Index)

JACC 2004,44:68-71JACC 2004,44:68-71

SA & Cardiac Resynchronization TherapySA & Cardiac Resynchronization Therapy

Eur Respir J 2006,26:95-100Eur Respir J 2006,26:95-100

6/10 have significantly reduced AHI6/10 have significantly reduced AHITwo thirds have reduced CSRTwo thirds have reduced CSR

• uncontrolleduncontrolled

• observationalobservational

• small samplesmall sample

SA & Cardiac Resynchronization TherapySA & Cardiac Resynchronization Therapy

Sleep Apnea :Sleep Apnea :SA & HypertensionSA & Hypertension

<0.001 <0.001 <0.002 <0.002

NEJM 2000;342:1378-84NEJM 2000;342:1378-84

HTN HTN + BMIHTN + BMI + Alc/smoking

(n=709)(n=709)

SA & HypertensionSA & HypertensionGreat population studiesGreat population studies

Wisconsin Sleep StudyWisconsin Sleep Study11: (n=709), follow up until 8 years: (n=709), follow up until 8 yearsSleep Heart Health StudySleep Heart Health Study22: (n=6841), follow up 3 years: (n=6841), follow up 3 years

1.1. N Engl J Med 2000;342:1378-84N Engl J Med 2000;342:1378-842.2. JAMA 2000;283:1829-36JAMA 2000;283:1829-36

The greater the severity of SA, the association with HTN is The greater the severity of SA, the association with HTN is increasedincreased

The question is: The question is: is there causality?is there causality?

SA & HypertensionSA & HypertensionPathophysiologyPathophysiology

Mirror effect

Rey et al. 2008Rey et al. 2008

SA & Pulmonary HypertensionSA & Pulmonary HypertensionThe controversy goes on…The controversy goes on…

RECOMMENDATIONSRECOMMENDATIONS

1.1. In the evaluation of pts with pulmonary HTN, evaluating SA In the evaluation of pts with pulmonary HTN, evaluating SA

is mandatory (evidence: low, yield: poor, class C)is mandatory (evidence: low, yield: poor, class C)

2. In the evaluation of pts with pulmonary HTN by SA, 2. In the evaluation of pts with pulmonary HTN by SA,

polysomnography is indicated (evidence: expert’s opinion, yield: polysomnography is indicated (evidence: expert’s opinion, yield:

intermediary, class B)intermediary, class B)

3. In the management of pts with SA, routine pulmonary HTN 3. In the management of pts with SA, routine pulmonary HTN

evaluation is evaluation is NOTNOT advised (evidence: low, yield: no, class I) advised (evidence: low, yield: no, class I)

4. In pts with SA and pulmonary HTN, CPAP reduces pulmonary 4. In pts with SA and pulmonary HTN, CPAP reduces pulmonary

pressure (but does pressure (but does NOTNOT normalize it) (evidence: low, yield: normalize it) (evidence: low, yield:

poor, class C)poor, class C)

Sleep Apnea & Sleep Apnea & Left ventricular hypertrophyLeft ventricular hypertrophy

• (n=53)(n=53)• RDI > 5, severe > 30RDI > 5, severe > 30• LVH: ♀ 110 g/mLVH: ♀ 110 g/m22 / ♂ 134 g/m / ♂ 134 g/m22

The link between SA and LVH could be The link between SA and LVH could be hypertension, however, hypertension, however, it is present in children and teenagers with SAit is present in children and teenagers with SA

Sleep Apnea & Sleep Apnea & Autonomous Nervous SystemAutonomous Nervous System

• (n=60)(n=60)• 3 grupos: AS severa, AS leve, control3 grupos: AS severa, AS leve, control• AS severa: AHI > 20AS severa: AHI > 20• Holter de 24 Hs con VFCHolter de 24 Hs con VFC

- Análisis en dominio de frecuencia- Análisis en dominio de frecuencia

- Análisis en dominio de tiempo- Análisis en dominio de tiempo• Ajustado para edad, BMI, FEyAjustado para edad, BMI, FEy

• ↓ ↓ parasympathetic toneparasympathetic tone• ↑ ↑ sympathetic tonesympathetic tone

Sleep Apnea & Sleep Apnea & Regulation of HRVRegulation of HRV

Am J PhysiolHeart Circ Physiol 2005;288:1103-12Am J PhysiolHeart Circ Physiol 2005;288:1103-12

3 mechanisms3 mechanisms

1.1. Vagal stimulus of pulmonary receptorsVagal stimulus of pulmonary receptors

2.2. Medullary control of respiratory centersMedullary control of respiratory centers

3.3. Baroreflex sensitivity (BRS)Baroreflex sensitivity (BRS)

↓ ↓ signivicant vagal afferencesignivicant vagal afference

(P<0.04)(P<0.04)

↓ ↓ significant BRSsignificant BRS

(P<0.03)(P<0.03)

Sleep Apnea & Sleep Apnea & Regulation of HRVRegulation of HRV

Intermittent chronic hypoxia (8 H-4 days):1. baroreflex sensitivity2. Total HRV (LF predominant)

Rey et al. 2008Rey et al. 2008

Sleep Apnea:Sleep Apnea:Diagnosis: PolisomnographyDiagnosis: Polisomnography

EMG

EEG

EOG

ECGSAT 02

Flow

Resp effort

Pulse

Differences between obstructive apnea and central apneaDifferences between obstructive apnea and central apnea

Sleep Apnea :Sleep Apnea :Treatment with CPAPTreatment with CPAP

• 12 randomized studies12 randomized studies• End point: reduction inEnd point: reduction inEpworth scoreEpworth score

> benefitin pts withAHI > 30

CPAP better than placebo (OR 2.94, p<0.001)CPAP better than placebo (OR 2.94, p<0.001)Heterogeneity – p<0.001Heterogeneity – p<0.001

Some ConclusionsSome Conclusions

1. Sleep Apnea is highly prevalent.

2. Associated with cardiovascualr diseases such as CHF, HTN, Obesity and

Metabolic Syndrome, Stroke, CAD, Autonomic Dysfunction, and Arrhythmias

3. Knowing the pathophysiological mechanisms permits starting multifactorial

treatments (lose weight, control HTN, prevent arrhythmias and infarctions).

4. Recognizing it allows treating it with C-PAP

5. Evidence indicates that rapid atrial pacemaking should NOT be universally

recommended.

6. In patients with apnea with CENTRAL origin, the treatment of cardiac

resynchronization remarkably improves apnea indices. This should be considered

when recommending this therapy.

If you want to contact me: adribaran@hotmail.com