Sleep Apnea: Sleep Apnea:

……the heart suffers even while sleeping…the heart suffers even while sleeping…

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 SymposiumNovember 2010November 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 cardiovascular diseaseThe link between SA and cardiovascular disease

5.5. Diagnostic yieldDiagnostic yield

6.6. Brief summary of managementBrief summary of management

7.7. Areas of investigationAreas of investigation

DefinitionsDefinitionsSleep ApneaSleep Apnea

1.1. SA:SA: a history of excessive sleepiness, frequent episodes of obstructing a history of excessive sleepiness, frequent episodes of obstructing

breathing during sleep, snoring, morning headaches, “arousals” + breathing during sleep, snoring, morning headaches, “arousals” +

polysomnography showing apneic episodes longer than 10 seconds polysomnography showing apneic episodes longer than 10 seconds

(at least 5 per hour)(at least 5 per hour)

2. 2. Apnea:Apnea: cessation of air flow, 0 cessation of air flow, 022 saturation reduction ≥ 4% saturation reduction ≥ 4%

► ► Central: alteration at CNS levelCentral: alteration at CNS level

► ► Obstructive: alteration at the upper respiratory wayObstructive: alteration at the upper respiratory way

3. 3. Hypopnea:Hypopnea: air flow reduction ≥ 30%, air flow reduction ≥ 30%, 02 saturation reduction ≥ 4%02 saturation reduction ≥ 4%

4. 4. AHI (Apnea/hypopnea index):AHI (Apnea/hypopnea index): amount of apneas & hypopneas per hour amount of apneas & hypopneas per hour

Sleep Apnea:Sleep Apnea:PathophysiologyPathophysiology

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

1.1. Sub-atmospheric intraluminal pressureSub-atmospheric 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. Physiological changes during sleepPhysiological changes during sleepa.a. In NREM stage: BP and HR reduction (10-20%): ↓ of CO and In NREM stage: BP and HR reduction (10-20%): ↓ of CO and

TPR, ↓ sympathetic tone in phase 4 of NREMTPR, ↓ sympathetic tone in phase 4 of NREMb. In REM stage: vasoconstriction + fluctuation of CO and HR b. In REM stage: vasoconstriction + fluctuation of CO and HR

2.2. Acute changes during SAAcute changes during SA

a.a. HR:HR: there are 2 possible patterns: there are 2 possible patterns:- 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 arousal and arousal (more frequent)(more frequent)-- Progressive bradycardia along the apnea

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

c.c. Cardiac Output:Cardiac Output: ↓ ejection volume during apnea along ↓ ejection volume during apnea along with intrapleural negative pressurewith intrapleural negative pressure

Pathophysiologic mechanisms Pathophysiologic mechanisms of cardiovascular morbidityof cardiovascular morbidity

Sleep Apnea

In summary…In summary…

SASA

Fluctuations of BP, HR and cardiac putput + 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 is the available evidence?What is the available evidence?

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 longer the apnea, the longer the bradycardia•No bradycardia in absence of SA

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

Polysomnography ECG recording is

represented by a single lead and at

times, it can be confusing. In this case,

the patient was referred due to 2:1 block

and in fact, the patient presented

RV outflow tract premature contractions.

Sleep Apnea:Sleep Apnea:Role for pacingRole for pacing

Physiologic pacing did not show benefits in patients with OSA

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

Associated mechanismsAssociated 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 with 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 interested in this topic…?Who is interested in this topic…?

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 refine theShould we refine theCHADSCHADS22 score? 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 association: 1. SA association: 55%55% 2. 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) association: SA (AHI>20) association: 53%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) association: SA (AHI>10) association: 55%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 polysomnographyAmbulatory polysomnography

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 & HypertensionLarge population studiesLarge population studies

Wisconsin Sleep StudyWisconsin Sleep Study11: (n=709), follow up 8 years: (n=709), follow up 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 HTNThe greater the severity of SA, the association with HTNincreasesincreases

The question is: The question is: Is there any causality?Is there any causality?

SA & HypertensionSA & HypertensionPathophysiologyPathophysiology

Mirror effect

Rey et al. 2008Rey et al. 2008

SA & Pulmonary HypertensionSA & Pulmonary HypertensionThe controversy remains…The controversy remains…

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:

intermediate, class B)intermediate, 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, children and teenagers with SA may develop LVH w/o having clinical HTNchildren and teenagers with SA may develop LVH w/o having clinical HTN

Sleep Apnea & Sleep Apnea & Autonomic Nervous SystemAutonomic Nervous System

• (n=60)(n=60)• 3 groups: Severe SA, mild SA, control3 groups: Severe SA, mild SA, control• Severe SA: AHI > 20Severe SA: AHI > 20• 24 Hs Holter with HRV24 Hs Holter with HRV

- Frequency domain analysis- Frequency domain analysis

- Time domain analysis- Time domain analysis• Adjusted for age,BMI, EFAdjusted for age,BMI, EF

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

Sleep Apnea & Sleep Apnea & HRV regulationHRV regulation

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)

↓ ↓ significant vagal afferencesignificant 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: PolysomnographyDiagnosis: Polysomnography

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. Identifying patients with SA allows treatment with C-PAP

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

recommended.

6. In patients with central sleep apnea, cardiac resynchronization remarkably

improves apnea indices. This should be considered when recommending CRT.

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