Prevalence and pathophysiology

1. Sleep disordered breathing:
prevalence and pathophysiology
Martin R Cowie
Professor of Cardiology
National Heart & Lung Institute
Imperial College London (Royal Brompton Hospital Campus)
m.cowie@imperial.ac.uk

2. Declaration of Interests
• Received research funding and consultancy/speaking
fees from ResMed, Servier, St Jude Medical,
Medtronic, Boston Scientific, Novartis, Pfizer, Alere,
Roche Diagnostics, Bayer
• Co-Principal Investigator for SERVE-HF

3. Daytime sleepiness no longer!

4. Johns MR. A new method of measuring daytime sleepiness:
The Epworth Sleepiness Scale. Sleep 14(6):540-545, 1991.
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5. OSA
CSR
CSA
60 seconds
100
%
70
100
%
70
100
%
70
Flow
Thorax
Abdomen
SaO2
Flow
Thorax
Abdomen
SaO2
Flow
Thorax
Abdomen
SaO2

6. Mechanical Effects of OSA on Heart Function
Kasai et al. J Am Coll Cardiol 2011;57:119–27
Inspiration effort with
occluded upper airway
Negative Intrathoracic
Pressure
Increased:
LV transmural pressure
LV afterload
RV pre-load
RV distension
Leftward septum
movement during diastole
Impaired LV filling
Reduced LV pre-load
Reduced stroke volume
UA = Upper Airway

7. Clinical observation
• ‘The only peculiarity in the last period of his illness, which
lasted only 8 or 9 days, was in the state of his respiration. For
several days his breathing was irregular; it would entirely cease
for a quarter of a minute, then it would become perceptible,
though very low, then by degrees it became heaving and quick,
and then it would gradually cease again. This revolution in the
state of his breathing occupied about a minute, during which
there were about thirty acts of respiration.’
William Stokes (1804-1878)
Treatise on the Diseases and Treatment of Diseases of the Chest (1837).

8. OSA
CSR
CSA
60 seconds
100
%
70
100
%
70
100
%
70
Flow
Thorax
Abdomen
SaO2
Flow
Thorax
Abdomen
SaO2
Flow
Thorax
Abdomen
SaO2

9. HF and mechanism of CSA
Prolonged circulation time
(Circulatory Delay)
SM Caples et al J Appl Physiol 2005; 99: 2433-2439
Increased CO2 sensitivity

10. Quantifying SDB
• Apnoea Hypopnoea Index (AHI)
o Number of apneas and hypopneas per hour
o Apnoea = cessation of flow for at least 10 sec
o Hypopnoea = 30% reduction of flow for at least 10 sec with a
4% O2 desaturation
o AHI < 5 (normal), AHI 5-14 (mild), AHI ≥ 15 (moderate/severe)
• Oxygen Desaturation Index (ODI)
o Number of O2 desaturations (of at least 4%) per hour

11. Is SDB common in HF?
• Vazir et al. 2007
• 55 men with CHF
• EF < 45%
• NYHA II
• Stable
• 53% SDB (AHI ≥ 15):
– 38% CSA
– 15% OSA
• Oldenburg et al. 2007
• 700 pts with CHF
• EF ≤ 40%
• NYHA II, III or IV
• Stable
• 51% SDB (AHI ≥ 15):
– 32% CSA
– 19% OSA
Oldenburg O et al. Eur J Heart Fail 2007; 9: 251-7Vazir A et al. Eur J Heart Fail 2007; 9: 243-50

12. SDB Prevalence by Gender and Age
n=190
* Woehrle H et al. BMC CV Disord 2014; 14: 46

13. Bitter et al. Eur J Heart Fail 2009
SDB prevalence in HFpEF
*
Prevalence of AHI
≥ 5 similar (70-
80%) to HFrEF

14. ©ResMed 2014 I
Prevalence of SDB in Acute HF
Average LVEF on admission 30%
80% had SDB (AHI>15) of whom 75% had CSA
Tremel et al., Eur Heart J 1999
*

15. But so what?

16. SDB in HF – French registry data
Damy T et al. Eur J Heart Failure 2012; 24: 1009 - 19

17. SDB in HF – French registry data
Damy T et al. Eur J Heart Failure 2012; 24: 1009 - 19
*Outcome: death or transplant or VAD

18. SDB in HF – German single-centre registry data

19. SDB in HF – risk of malignant ventricular arrhythmias
Cut off AHI ≥ 15/h
Bitter T P et al. Eur Heart J 2011; 32: 61-74

20. Cut off AHI ≥ 15/h
SDB in HF – risk of malignant ventricular arrhythmias
Bitter T P et al. Eur Heart J 2011; 32: 61-74

21. SDB in HF – risk of malignant ventricular arrhythmias
Bitter T P et al. J Cardiovasc Electrophysiol 2013; 24: 1132 – 40

22. SDB in HF – risk of malignant ventricular arrhythmias
Bitter T P et al. J Cardiovasc Electrophysiol 2013; 24: 1132 – 40

24. SERVE-HF StudySERVE-HF Study
Treatment of sleep-disordered breathing with
predominant central sleep apnoea by adaptive
servo ventilation in patients with heart failure
NCT 00733343

25. • 1325 patients with HFrEF
and predominantly central
sleep apnoea randomised
• 651+ events (All cause
mortality + HF admissions)
• Results under consideration
with NEJM
Eur J Heart Failure 2013; 15: 937 – 43
STOP press

26. Safety note issued 13 May 2015
• “The preliminary primary results show no significant difference between
patients treated with ASV and those in the control group for the primary
endpoint:
– time to all-cause mortality or unplanned hospitalization for worsening heart
failure (HR =1.136 [0.974 - 1.325], p=0.104).
• However, there was a 2.5% absolute increased annual risk of cardiovascular
mortality for those randomized to ASV therapy compared to the control
group:
– 10% of the ASV group experienced a CV death each year compared to 7.5% of the
control group, (HR=1.335 [1.070-1.666), p=0.010).
• The increased risk appears to be greater in those with more severe
ventricular dysfunction
• The majority of excess mortality is due to death occurring out of hospital
(likely sudden cardiac death). The risk does not diminish with time on therapy
and is independent of perceived symptomatic benefit from therapy.”

27. CSR: Risk factor, risk marker or compensatory
mechanism??