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Welcome local and national attendees to the
first ACRA WEBINAR
Sleep Disordered Breathing:
A Cardiology Condition –
A Sleeping Killer
Dr Philip Currie
MBBS, FRACP, MBA - Cardiologist and Echocardiographer
Local attendees
- Emergency exits
- Toilet location
- Mobile phones (please switch off or turn to silent)
- Evaluation forms
National attendees
- Questions can be typed in left hand side text box
- These will be addressed during the presentation
- Evaluation to be completed on your screen on completion of
event.
Next ACRA Webinar THURSDAY 25TH JUNE 2015 - Omega 3 in Cardiovascular
Disease Prevention: New Evidence on an old intervention
Welcome to country
I would like to pay my respects to the
Traditional Owners of the land on which we
are meeting today. I would also like to pay
my respects to elders both past and present.
Sleep
Important In Wellness and In Disease
Sleep Disordered Breathing (SDB)
Not Just a Sleep Disorder
Heart Condition & Sleeping Killer
Maslow’s Hierarchy of Needs
Sleep Is Important
Sleep Is Part of Wellness
Important to Quality of Life
Physiological Effects of Sleep
Active physiological state - body repair & variety of important functions:
Learning and Memory
Important for consolidation of new information & memory formation
Growth and Development
Secretion of growth hormone & prolactin increased during sleep
Blood Pressure
Chronic short sleep duration increases the risk of hypertension in adults
Stress and Metabolism
Cortisol & thyrotropin (thyroid stimulating protein) decrease during sleep
Appetite Management
Ghrelin & leptin hormone levels influence hunger & satiety
Obstructive Sleep Apnea
Sleep Disordered Breathing (SDB)
More Than OSA - A Social Condition
Disease Severity & Lack of Recognition
Social Condition
Snoring
Daytime Sleepiness
OSA
CPAP
Retail CPAP
Sleep Dr
CV Morbidity & Mortality
AF
HT
CAD
CHF
Stroke
Mixed
CSA
ASV
Cardiology
What is Sleep-Disordered Breathing?
OSA, CSA, and Mixed Sleep Apnea
Flow
OSA
Thorax
Abdomen
SaO2
100
%
70
Effort
Flow
CSA
Thorax
Abdomen
SaO2
100
%
70
No Effort
60 sec
Physiological Consequences of Sleep Apnea
Plunging blood
oxygen
saturation
Negative swings
in intra-thoracic
pressure
Increase in
blood pressure
Surge sympathetic
nerve activity
Morgan et al., 1996 Sleep
How Do We Measure SDB?
Apnea-Hypopnea Index
•
Based on the total number of complete cessations
(apnea) and partial obstructions (hypopnea) of
breathing occurring per hour of sleep
•
These pauses in breathing must last for 10 seconds
and are associated with a decrease in oxygenation
of the blood >3%
•
AHI can be used to classify the severity of disease
• Mild 5-15
• Moderate 15-30
• Severe >30
Question
Why is Sleep Disordered Breathing
important in Cardiovascular and
Metabolic Diseases?
Obesity: A Global Epidemic
The Big Elephant (Sumo) in the Room
Obesity is Now Socially Accepted
Risk Factors for Co-Morbidities
Cardiovascular Disease
Hyperlipidemia
Diabetes
Hypertension
Obesity
OSA
Sleep Apnea Prevalence in CV Disease
Ubiquitous
80%
70%
35%
Logan et al.
J. Hypertension 2001
Einhorn et al.
Endocrine Prac 2007
50%
Javaheri et al.
Circulation 1999
50%
Somers et al.
Circulation 2004
Sjostrom et al.
Thorax 2002
30%
Schafer et al.
Cardiology 1999
30%
Sanner et al.
Clin Cardiology 2001
Cardiovascular Disease Continuum
Adapted from Dzau et al, 2006 Circulation
Sleep Apnea – A Cardiovascular Disease
Jean-Louis et al., 2010 Expert Rev. Cardiovasc. Ther.
SDB and Mortality
• 6,294 participants
• Average follow up period = 8.2 years
• 1.46 X more likely TO DIE with severe SDB
• Predictor of mortality – nocturnal hypoxaemia
Punjabi et al., 2009 PLoS Medicine
Wisconsin Sleep Cohort – 18 year Follow up
n = 1396
Young et al., 2008 SLEEP
Long Term Fatal and Non-fatal CV Events
Worse with More OSA & Better with CPAP
• 200-400 subjects per group
• Followed for a mean of 10.1 years
Marin et al., 2005 Lancet
Cumulative Incidence of Hypertension
Worse With More Severe OSA
n = 1889
Marin et al., 2012 JAMA
Atrial Fibrillation and SDB
•
Multiple mechanistic factors contribute to SDB
suggesting SDB induces AF
•
High incidence of OSA in patients with AF
•
High incidence of recurrence of AP in first year
post DC cardioversion in pts not Rx with CPAP
•
Risk factor modification reduces recurrent AF post
AF ablation (symptoms, AF burden, recurrent
ablation)
The ARREST-AF Cohort Study
Aggressive Risk Factor Reduction Post AF Ablation
Pathak et al J Am Coll Cardiol 2014;64:2222
Single-procedure, drug-free, AF-free & Total AF-free Survival
Pathak et al J Am Coll Cardiol 2014;64:2222
Obstructive Sleep Apnea and the
Risk of Sudden Cardiac Death (SCD)
•
10,701 consecutive adults first PSG 1987-2003
•
15 yr follow up SCD - average follow-up of 5.3 yrs, 142 pts
had resuscitated or fatal SCD (annual rate 0.27%)
•
Independent risk factors for SCD - age, hypertension,
CAD, cardiomyopathy, heart failure, ventricular ectopy or
nonsustained VT, & lowest nocturnal O2 sat
•
SCD was best predicted by age >60 years (HR: 5.53), AHI
>20 (HR: 1.60), mean nocturnal O2sat <93% (HR: 2.93), &
lowest nocturnal O2 sat <78% (HR: 2.60; all p < 0.0001)
J Am Coll Cardiol 2013;62:610–6)
Obstructive Sleep Apnea and the
Risk of Sudden Cardiac Death
J Am Coll Cardiol 2013;62:610–6)
Obstructive Sleep Apnea and the
Risk of Sudden Cardiac Death
J Am Coll Cardiol 2013;62:610–6)
Effect of OSA in Metabolic Syndrome
Bonsignore MR et al ERJ 2012
Summary
Sleep Disordered Breathing Increases Mortality
• CARDIOVASCULAR
– SDB is very common and affects prognosis
– Cardiovascular diseases are probably the most
important consequence of OSA
– Assessment of SDB is rapidly becoming a routine
part of the management of cardiology patients
• DIABETES
– OSA and type 2 diabetes frequently coexist
– Accumulating evidence that OSA impairs glucose
metabolism
– Rapidly increasing awareness of OSA in the
diabetes community and assessment/management
should INCREASE
31
© ResMed 2012 07
Where Else to
Go
In Heart Failure?
Well, this is just going
from bad to worse!
32
Lets Invite A Colleague and Sleep On It
© ResMed 2012 07
Outline
•
Heart failure – big problem, need more Rx
•
Traditional Epiphenomena - LBBB, AF
•
Sleep Disordered Breathing – more than OSA
? another epiphenomenon
•
ASV – Adaptive Servo Controlled Ventilation
•
Schal-HF Registry
•
SERVE-HF Trial
Heart Failure
•
300,000 patients in Australia have CHF
•
Despite recent advances in treatment CHF
continues to cause debilitating symptoms
•
Congestive heart failure leading cause of
hospitalisation in >65 years
•
CHF costly with frequent hospital admissions and
deadly. 5 year mortality remains high at 50%
Heart Failure – We Need More !
•
New interventions that reduce symptoms,
increase quality of life, reduce hospital
admissions and mortality are needed
•
It is likely that new interventions will be targeted
at specific subgroups of chronic HF patients
rather than all CHF pts
Heart Failure Management
Primary Cardiac Problem
Blocking RAS
(ACE, ARB, Spironolactone)
Blocking SNS
(Beta Blocker)
LBBB
Atrial fibrillation (PVI)
SDB (ASV)
Add-on Therapy in Heart Failure
Each Added Therapy Incrementally Decreases Mortality
CHARM
AR2B
?? ASV
Therapy
for SDB
?? LVAD
Destination
Therapy
There remains a 50% 5 year mortality
Biventricular Pacing
Resynchronising Therapy
Current Clinical Trajectory of Patients with HF
I
II
Major costs are incurred for each
acute cardiac decompensation
inpatient hospital admission
III
IV
Acute events
Death
Death
Optimal Medical Management
time
LVAD – Left Ventricular Assist Device
• Bridge to Transplant
• Destination Therapy
• Bridge to Recovery
• LVAD starting to approach transplant survival in
pts not previously transplant candidates
SBD
International Cardiology Guidelines Committee
Sleep Disordered Breathing in Cardiology & CHF
“We Await the Evidence of CV Mortality RCT”
Why is The Disconnect?
The Elephant in The Room
•
Often OSA overlooked as a reversible CV risk factor
• No large-scale, multicentre, randomised control trials
of PAP therapy (cholesterol – pre statin)
• Ethical challenges (long term no active treatment for
symptomatic OSA at risk for car accidents)
• Reduced adherence in nonsleepy pts
•
CSA is indeed Silent But Deadly as the clinical markers
of OSA (snoring, witnessed apnoea, daytime sleepiness)
are not common
• No positive mortality RCT
Principal Mechanisms Contributing to
SDB in CHF - Important Differences
Central Sleep Apnea
•
•
•
Pulmonary vagal
afferent receptor
stimulation
Increased central
chemo-responsiveness
Abnormal
cerebrovascular
reactivity to pCO2
Obstructive Sleep Apnea
•
Obesity
•
Reduced neural output
to upper airway
muscles
•
Pharyngeal oedema
•
Upper airway
anatomical
abnormalities
Bad Cardiovascular Autonomic Effects of OSA
Kasai, T. et al. J Am Coll Cardiol 2011;57:119-127
OSA - All Roads Lead to HF
Brisco et al., Curr Heart Fail Rep 2010
Pathophysiologic Consequences of CSA in Heart Failure
J Am Coll Cardiol. 2015;65(1):72-84
SchlaHF Registry of the SERVE-HF Trial
High Prevalence of SDB in CHF
•
High prevalence of SDB (46%) in stable chronic
HF patients
•
Male gender, age, BMI, severity of both symptoms
and LV dysfunction clinical predictors for SDB
•
Chronic HF patients with SDB often do not show
characteristic SDB symptoms
•
Presence of one or more predictors of SDB (e.g.
male, older, obesity, LVEF <25%, NYHA class
III/IV or AF) should prompt clinicians to perform
device-based screening for SDB
Risk factors for SDB in Chronic HF
Gender, Age , AF, High BMI Low LVEF
-
Prevalence of SDB in Stable CHF
Populations
SchlaHF Registry: PSG data
CSA prevalence increases with worsening LV systolic function
and increasing NYHA
ASV Keywords
Adaptive Servo-Ventilation
Adaptive: the (pressure) target is adjusted
according to the input from the patient, i.e. the
target is not a fixed value but instead adapts to
patient’s demand
Servo-ventilation: closed feedback loop where
therapy is designed to achieve a target
ventilation
(PPM analogy: CPAP =PPM, ASV=PPM, ICD)
Adaptive Servoventilation
ASV Auto
Flow
APNEA
ASV
HYPOPNEA
Key Principals of Adaptive Servo-Ventilation ASV
•
Used to regulate or maintain normal ventilation by
correcting the ventilatory pattern of a patient with
central sleep apnea (CSA and/or Cheyne-Stokes)
•
Specifically by:
• Stabilizing the upper airway when required, by
offering a base level of pressure (EPAP)
• Deliver pressure support to stabilise ventilation
• Provide patient-machine synchrony
How the ASV Determines a Target
weighted average mean (3 min)
•
•
On a breath by breath basis minute ventilation is
calculated
Minute ventilation is monitored using a weighted
average mean (3 min window)
How the ASV Determines a Target
weighted average mean (3 min)
•
On a breath by breath basis minute ventilation is calculated
•
Minute ventilation is monitored using a weighted average mean (3
min window) – continually adjusting across the night
•
Calculates 90% of minute ventilation – target ventilation
•
If instantaneous minute ventilation < target ventilation ( PS)
•
If instantaneous minute ventilation > target ventilation ( PS)
After ~10-30 mins…
Breathing
normalised…
…and SpO2
stable
PAP Therapy in CSA
ASV Abolishes CSA
Teschler H et. al; AJRCCM 2001
HF – ASV and AHI Meta-Analysis
Reduction in AHI
Sharma et al., 2012 CHEST
HF – ASV and LVEF
Improvement in LVEF
Sharma et al., 2012 CHEST
Pts With Severe Advanced Heart Failure –
ASV Decreases CHF Events:
A Pooled Meta Analysis Of 629 Pts With CSA
J Am Coll Cardiol. 2015;65(10_S)
Current Clinical Trajectory of Patients with HF
I
II
Major costs are incurred for each
acute cardiac decompensation
inpatient hospital admission
III
IV
Acute events
Death
Death
Optimal Medical Management
time
Current Clinical Trajectory of Patients with HF
I
Patient with Cheyne Stokes Respiration
Prognosis poor
II
Trajectory without
Cheyne Stokes
III
IV
Death
Acute events
Optimal Medical Management
Death
Death
time
Possible Trajectory of HF Patients using ASV
Potential for Dramatic Improvement in Economics of
Management of Cardiac Failure
Patient with Central Sleep Apnea
I
Trajectory without
Central Sleep Apnea
II
III
*ASV?
IV
Acute events
Death
Death
Routine Clinical Management
time
*Await final results of SERVE-HF trial & the ADVENT-HF trial late 2016
Treatment Of SDB In Pts Admitted For
Decompensated HF Reduces 6 Mth Hospital Visits
•
64 patients admitted with CHF underwent PSG
within 4 weeks discharge
•
60yrs old, BMI 38, 48% male, mean AHI 33
•
29/59 pts (49%) compliant PAP therapy
•
mean change in hospital visits decreased to 0.7 ± 1.8 visits compliant group vs mean
increase of 0.2 ± 1.8 visits for the noncompliant group (paired Wilcoxon test, p=0.03)
J Am Coll Cardiol. 2015;65(10_S)
SERVE-HF Study
Treatment of sleep-disordered
breathing with predominant central
sleep apnea by adaptive servo
ventilation in pts with heart failure
SERVE-HF
Design
•
Randomised, multi-centre, outcome study
•
Parallel group design, comparing control
(optimal medical management) with active
treatment (optimal medical treatment plus
adaptive servoventilation).
•
Sample size: approx. 1260 patients
•
80 active centres
•
Estimated 20% drop out rate
•
Estimated minimum follow up of 24 months.
SERVE-HF-Study
Inclusion Criteria
 Chronic heart failure
 LVEF <45%
 NYHA class III or IV
 Optimised medical treatment
 SDB (AHI ≥ 15/h) with > 50% central events and
a central AHI ≥ 10/h
SERVE-HF-Study
Preliminary Results
•
1325 pts
•
Primary end point – All cause mortality or
hospitalisation NS difference
•
Preliminary analysis – significant 2.5% absolute
increase in CV mortality in ASV Rx group (10%
ASV vs 7.5% per year in control group)
•
Current ResMed response - avoid ASV in patients
who fulfill entry criteria of SERVE-HF trial
•
Awaiting detailed analysis
Summary
Sleep is Important in Wellness and In Disease
• SDB is very common and increases mortality
• CV diseases the most important consequence of OSA
• Recognition and management of SDB must become
routine in the management of cardiology pts
• SDB diagnostics in CV patients (PSG, home based PSG
and type 3 screeners)
• CSA needs to be recognised due to its prevalence,
cheap effective treatment (by cardiology standards)
• Greater understanding of ASV – will have greater use
• Await cardiology trials (large randomised trials with
hard end points (mortality and hospitalisation)
• Sleep and SDB major consideration in the holistic
management of pts
Final Message - Connect the Dots
Specifically SDB is a CV Problem Which Kills
It must be considered, diagnosed & aggressively managed