Clinical year in review

Sleep disorders

Antalya, April 26, 2007

Prof. J. Verbraecken

Antwerp University Hospital

Belgium

Johan.verbraecken@uza.be

Clinical year in review: sleep disordersIntroduction

The most important developments in respiratory sleep medicine last year relate to the interaction between the respiratory and cardiovascular systems in patients with SRBD.– CV complications of obstructive sleep apnoea

syndrome (OSAS): prevalence and mechanisms– Congestive heart failure with sleep apnea– Impact of CPAP therapy on CV outcomes

Pathogenesis of OSA Diagnosis of OSA Treatment of OSA

CV complications of OSA CV disease represents the principal physical

morbidity and probable mortality from OSAS. – Hypertension– Ischaemic heart disease– Cerebrovascular disease

The precise mechanisms are unclear but are likely to be multifactorial– Pathophysiologic, neurologic and cell/molecular

mechanisms likely play a role.

CV complications (and alterations) of OSARight ventricular function

Shivalkar B et al JACC 2006; 47(7): 1433-9

CV complications (and alterations) in OSARight ventricular function

Shivalkar B et al JACC 2006; 47(7): 1433-9

CV complications (and alterations) in OSA

RV:Effect of CPAP

Shivalkar B et al JACC 2006; 47(7): 1433-9

CV complications (and alterations) in OSA AHT: effect of CPAP

Robinson GV et al Eur Respir J 2006; 27:1229-1235

35 nonsleepy, hypertensive OSA

CV complications (and alterations) in OSA AHT: effect of CPAP

Therapeutic vs sham-placebo CPAP

Robinson GV et al Eur Respir J 2006; 27:1229-1235

CV complications (and alterations) in OSA CAD

Peker Y et al Eur Respir J 2006:28: 596-602

Sleep clinic Cohort without concomitant heart disease at inclusion in 1991

8 years follow-up; n=308

Peker Y et al Eur Respir J 2006:28: 596-602

Incidence of CAD at follow-up

OSA

Non OSA

Peker Y et al Eur Respir J 2006:28: 596-602

Predictors of CAD: time since baseline; current age; SaO2 min; asthma/COPD at baseline; efficient OSA treatment (inverse effect)

!! Risk x 6

Peker Y et al Eur Respir J 2006:28: 596-602

Impact of

CPAP

CV complications (and alterations) in OSA AMI

Tsukamoto K et al Circ J 2006;70:1553-1556

CV complications (and alterations) in OSA Incident AF

Gami AS et al JACC 2007;49(5):565-571

CV complications (and alterations) in OSA Incident AF

Gami AS et al JACC 2007;49(5):565-571

CV complications (and alterations) in OSA Incident AF

Gami AS et al JACC 2007;49(5):565-571

Congestive Heart Failure with sleep apneaImpact on sleep quality

Hastings PC et al Eur Respir J 2006;27:745-755

Congestive Heart Failure with sleep apnea

Hastings PC et al Eur Respir J 2006;27:745-755

TIB SL SEI

Daytime activity

Congestive Heart Failure with sleep apnea Use of acetazolamide

Javaheri S. AJRCCM 2006; 173: 234-7

Congestive Heart Failure with sleep apnea Use of acetazolamide

PlaceboPlacebo ACETACET pp

CAICAI 4949 2323 0.0040.004

Javaheri S. AJRCCM 2006; 173: 234-7

Complex sleep apnea syndrome (CompSAS) Definition: a group of patients with OSAS who develop a high

frequency of central apneas and/or a disruptive Cheyne-Stokes respiration (CSR) pattern after application of CPAP

Complexitiy which may not be unmasked until application of CPAP

Prevalence: 34 on 223 (15%) Predominantly male patients

– Low OAI during CPAP

– Fairly similar patients respond differently to CPAP

– No clinical differences with OSA or CSA

– Trend towards longer apnea duration in the patients with CompSAS Hypothesis: More instability in respiratory and/or cardiovascular

control at baseline than patients with OSA

Morgenthaler TI et al Sleep 2006,29(6):1203-1209

Management of Complex sleep apnea

CPAP not effective BIPAP ? ASV ?: at least worthwhile to evaluate

Sleep Medicine 2006;7:474-479

Pathogenesis OSA and diabetes

V. Viot-Blanc, P. Levy. Sleep Medicine 2006:538-540

N=938 men (general practice databases) Definition OSA: ODI>10 23% had OSA ! Confirmed by PSG

West SD et al, Thorax 2006;61:945-950

Veasey S et al Sleep 2006; 29(3):280-281

Increased levels of AGE in nondiabetic OSA

Tan K et al Sleep 2006;29(3):329-333

Pathogenesis OSA and antioxidants

Barcelo A et al Eur Respir J 2006;27:756-760

Pathogenesis: OSA and antioxidants

Barcelo A et al Eur Respir J 2006;27:756-760

Antioxidants and HCVR: harmfull ?

Zakynthinos S et al AJRCCM 2007;175:62-68

HCVR 1.70.4 3.2 0.5 l/min/mmHg

200 mg Vit E; 50.000 IU Vit A; 1g Vit C; 600 mg allopurinol; 2 g NAC

Pathogenesis: OSA and antioxidantsImpact of Vit C: beneficial ?

Grebe M et al AJRCCM 2006;173:897-901

Vit C and FM vasodilation

Beneficial effect of Vit C in OSA group ?

Solh AA et al ERJ 2006;27:997-1002

N=12 2 w 300 mg allopurinol compared to placebo Less oxidative stress and increase in FMD

Pathogenesis: OSA and antioxidantsImpact of CPAP

Barcelo A et al Eur Respir J 2006;27:756-760

=

Pathogenesis: sleep apnea and pre-eclampsia

Yinon D et al ERJ 2006;27:328-333

Pathogenesis: Intraocular pressure before and during CPAP

average 24 hour IOP in OSA

13,0

14,0

15,0

16,0

17,0

18,0

19,0

20,0

21,0

22,0

12 14 16 18 20 22 0 2 4 6 8 10

time of measurement (h)

IOP

mm

Hg no CPAP

CPAP

Kiekens S et al, IOVS

Descent from mountains to sea level : AHI 53 4733 mmHg In some even normalisation of AHI

Chest 2006;130:1744-50

Diagnosis: Functional imaging of the UA Computational Fluid Dynamics in OSA

Creation patient specific 3D-computer model

Grid of the upper airway

Visualisation of flow contours resistance can be calculated

Conversion of a CT scan of the UA into a CAD model

Diagnosis: Functional imaging of the UA Computational Fluid Dynamics in OSA

Sung SJ et al. Angle Orthod 2006;76:791-9 Vos W et al J Biomech 2007, in press.

Diagnosis: Development of single channel portable SDB diagnostic device

Certain commercially available pacemakers have a trans-thoracic impedance sensor primarily intended to adjust pacing rate during exercise upon changes in minute ventilation

Pace 2006;29:1036-43

Diagnosis: development of single channel portable SDB diagnostic device

Pace 2006;29:1036-43

Diagnosis: CPAP treatment trial over 2 W as an initial diagnostic test in comparison with PSG

Prediction of OSA: sensitivity 80%, specificity 97%, PPV 97%, NPV 78%

PSG could be avoided in 46% of the patients

Senn O et al, Chest 2006;129:67-75

Treatment: CPAP Compliance Addition of hypnotics ?

Bradshaw DA et al Chest 2006;130:1369-1376

N=72 Hypnotic vs placebo vs standard care

Treatment: CPAP Compliance Addition of hypnotics ?

Bradshaw DA et al Chest 2006;130:1369-1376

Treatment: Long-term CPAP compliance

Sucena M et al Eur Respir J 2006;27:761-766

Treatment: Long-term CPAP compliance

Sucena M et al Eur Respir J 2006;27:761-766

5h20min

6h40min

Treatment When do patients interrupt CPAP therapy ?

Sucena M et al Eur Respir J 2006;27:761-766

N=110 patients 82% discharged on the day of surgery Admission: due to pain and nausea UPPP can be carried safely on an outpatient

basis.

Otolaryngol Head and Neck Surgery 2006, 134:542-544

Treatment: UPPP

Using a pacemaker night heart-rate feature that allows programming of heart rates separately during the night and day

NOP followed by a reduction in circulation time did not improve AHI in patients with OSA.– 1 week: Melzer C et al, Sleep 2006;29(9):1197-1202– 1 night: Krahn AD et al, J Am Coll Cardiol 2006;47:379-83

Treatment: overdrive pacing

Sleep: Impact of sleep quality and quantity

Gangwisch JE et al Sleep 2005;28(10):1289-1296

Gangwisch JE et al Hypertension 2006;47:833-839

N=4810 patients. Sleep durations of <5h per night were associated with a significantly increased risk of hypertension (HR 2.1) in subjects between the ages of 32 and 59 years, signficant after controlling for obesity and diabetes

2813 men, 3097 female Usual sleep duration above or below the median of 7

to 8 hours per night is associated with an increased prevalence of hypertension, particularly at the extreme of less than 6 hours per night.

Gottlieb D et al, Sleep 2006, 29(8):1009-14

Sturm R. Public Health 2007

Obesity: Increases in morbid obesity in the USA: 2000-2005

Accreditation of sleep medicine centres

J Sleep Res 2006;15:230 J Sleep Res 2006;15:231-238