Apnea-Hypopnea- Index The new old biomarker for Sleep-Disordered Breathing Alan S Maisel MD
Triumvirate of Health-public awareness 1.8% Sleep Physical Fitness Nutrition 91.3% 99.9%
Sleep is important to health because it allows for metabolic restoration of the brain and body. Changes in digestion function Growth hormone secretion Alterations in breathing (slow & shallow)
Importance of Learning about Sleep Apnea Sleep apnea is a serious health problem impacting about 20% of US adults 1 75% of severe sleep apnea patients are undiagnosed 2 Clinical studies show treating sleep apnea can: 3-6 reduce blood pressure improve left ventricular ejection fraction improve insulin sensitivity
PREVALENCE
Estimated Obstructive Sleep Apnea (OSA) US Population 100% 90% 80% 70% 60% 307M 52M OSA Population 255M Non-OSA Population 52M 12M Severe OSA 11M Moderate OSA 23M 4.1M Diagnosed 18.9M Undiagnosed 4.1M 3.3M CPAP 50% 40% 29M Mild OSA (AHI 5-15) 30% 20% 10% 0% Total US Population Segments of OSA Population Addressable OSA Population 0.4M Device: Rx/OTC 0.2M 0.2M Treatment of Diagnosed Surgery Untreated 7 Source: McKinsey & Company analysis; Harvard Medical School, 2010
OSA Prevalence in Cardiovascular Disease Drug Resistant Hypertension 1 83% Congestive Heart Failure 2 76% Pacemakers 3 59% Atrial fibrillation 4 49% All hypertension* 5 Coronary artery disease* 6 30% 37% Angina 7 31% * Male Subjects Only 0 20 40 60 80 100 1 Logan AL et al. J Hypertens 2001 2 Oldenburg O et al. Eur J Heart 2007 3 Garrigue S et al. Circulation 2007 4 Gami AS et al. Circulation 2004 5 Sjostrom C et al. Thorax 2002 6 Schafer H et al. Cardiology 1999 7 Sanner BM et al. Clin Cardiol 2001 8
Common Sleep Apnea Risk Factors Obesity Physical inactivity Increasing age Cardiovascular Smoking Sleep apnea Endocrine and metabolic Male gender Alcohol or sedative use Family history of sleep problems Anatomic abnormalities of the upper airway
The two-headed patterns of SDB in HF OSA CSA
Types of SDB: OSA Obstructive sleep apnoea (OSA): Most common type of SDB Caused by recurrent collapse of the upper airway Causes intermittent hypoxia, negative intrathoracic pressure swings, sympathetic activation, systemic inflammation, oxidative stress Flow Thorax Abdomen SaO 2 100 % 70 60 sec Cowie et al. Eur Cardiol Rev 2015.
Types of SDB: CSA Central sleep apnoea (CSA): Flow Dysregulation of respiratory control (lack of drive to breathe during sleep) Repetitive periods of reduced ventilation May manifest at CSR (central apnoeas alternating with periods of crescendo-decrescendo respiratory tidal volume) Causes increases sympathetic nervous system activity, greater cardiac electrical instability, low frequency oscillations in heart rate and blood pressure Thorax Abdomen SaO 2 100 % 70 60 sec Cowie et al. Eur Cardiol Rev 2015.
Sleep Apnea The Basics Apnea Hypopnea Index (AHI) Number of apneas and hypopneas per hour Apnea = cessation of flow for at least 10 sec Hypopnea = 30% reduction of flow for at least 10 sec with a 4% O 2 desaturation AHI < 5 (normal), AHI 5-14 (mild), AHI 15 (moderate/severe) Oxygen Desaturation Index (ODI) Number of O 2 desaturations per hour Based on 4% drop in baseline
Mechanism of Normal Breathing Breathing is regulated by: Chemoreceptors that monitor blood gas levels CO 2 (primarily) and O 2 (secondarily) The respiratory control center in the brain ResMed 2014
Mechanism of OSA What happens in OSA patients: Airway is obstructed The level of CO 2 rises (O 2 level falls), signaling patient to breathe
Obstructive Sleep Apnea (OSA) Indicators Habitual loud snoring Witnessed apneas Hypertension Excessive daytime sleepiness Obesity/ neck circumference Morning headaches Heart failure/ CVD
Mechanism of CSA What happens in CSA patients: Airway is open Because the level of CO 2 is below the patient s apneic threshold, no signal is sent to breathe
Crossing the Threshold What is the apneic threshold? When a patient s CO 2 level falls below normal range and enters the apneic threshold, a central apnea occurs. Breathing is normal Central apneas occur
Patient Video (OSA)
Pathophysiological Effects of OSA Arousal: HR & BP Minute ventilation Neurohormonal imbalance Sleep fragmentation Sleep Fragmentation sleep debt: Neurohormonal imbalances Behavioral changes Intrathoracic pressure changes: Overdistends R atrium and ventricle Shifts intraventricular septum to left Afterload Cardiac output Desaturation (hypoxemia): Sympathetic response HR & BP Arrhythmias coagulability and clot formation Deoxygenation-reoxygenation causes endothelial dysfunction
Cardiovascular Disease Development OSA Disease Mechanisms Associated CV Disease Hypoxemia Reoxygenation Hypercapnia Intrathoracic pressure Arousals Sleep deprivation Sympathetic activation Metabolic dysregulation Left atrial enlargement Endothelial dysfunction Hypercoagulability Hypertension Heart failure Arrhythmias Renal disease Stroke Myocardial infarction Sudden Cardiac Death 22 Somers et al. Circulation 2008;118:1080-111
SDB in Heart Failure Prevalence rates of 50-75% 1 More common than in the general population With preserved (HFpEF) or reduced (HFrEF) ejection fraction Relative lack of typical symptoms (especially daytime sleepiness) 7 Lack of recognition and diagnosis
OUTCOMES
AJRCCM 2011
Survival SDB in HF Cut off AHI 15/h Bitter et al., Eur Heart J 2010
CSA and Mortality in HF Jilek et al., EJHF 2011
CSA Predictor Cardiac Readmission Khayat et al., J Cardiac Fail 2012
TREATMENT
Treatment Theories for CSA/CSR Oxygen Addition of deadspace or rebreathing of CO 2 Respiratory stimulants Diamox Sleep repositioningencouraging non-supine positioning Modest reduction in apneas, but does not improve CHF events, but may minute ventilation; can cause respiratory acidosis; can arousals events but doesn t SaO 2, arousals or improve sleep structure; many adverse side effects, specifically arrhythmias Results in acidosis & in ventilation while fluid retention May CSA, though improvements are likely to be seen only in NREM sleep
Pressure Pressure Pressure PAP Therapy CPAP Time Automatic Positive Airway Pressure (APAP) Therapy Time Bilevel Time
Malhotra et al., NEJM CPC 2003
Why Bilevel Therapy is Often Ineffective CSA/CSR pts have low CO 2 Bilevel, with varying levels of PS, increases ventilation Breathing increases, CO 2 levels drop further CSA/CSR persist s or worsens ResMed 2014
What is ASV? Adaptive servo-ventilation (ASV) is a non-invasive ventilatory therapy that supports inspiration when breathing amplitude is reduced and ensures sufficient respiration when respiratory effort is absent (variable IPAP) Upper airway patency is ensured by provision of endexpiratory pressure (fixed or variable EPAP) Patient Flow Apnoea Hypopnea ASV Cowie et al. Eur Cardiol Rev 2015.
ASV vs Other PAP THERAP Y AIM FEATURES PRESSURE PROFILE CPAP Maintain upper airways open Fixed or automatically adjusted expiratory pressure APAP Maintain upper airways open Continually adjusting expiratory pressure to optimal level for specific patient needs BPAP ASV Support breathing in lung diseaserelated respiratory insufficiency Maintain upper airways open Fixed expiratory pressure and pressure support at inspiration, usually with fixed backup rate Continually adjusting expiratory pressure to optimal level according to specific patient needs APAP, auto-adjusting positive airway pressure; ASV, adaptive servoventilation; BPAP, bilevel positive airway pressure; CPAP, continuous positive airwa Cowie et al. Eur Cardiol Rev 2015.
ASV and Minute Ventilation ASV responds to changes in minute ventilation Monitors recent average minute ventilation (~3-min window) It continuously calculates a target ventilation throughout the night (90% of recent average ventilation) Adjusts pressure support up or down as needed to achieve target 3 min moving window
Bilevel device in CPAP Mode CSR Pattern SpO 2 variable 90-98% Pulse rate variable 77-91 beats per min
Switch from CPAP to ASV mode Respiratory pattern beginning to normalize SpO 2 stabilizing Less variability in pulse rate
Respiratory pattern completely normalized SpO 2 stable 94-97% Pulse rate stable 73-77 beats per min
SERVE HF: Objective To investigate the effects of adding ASV to guideline-based medical management on survival and cardiovascular outcomes in patients with heart failure with reduced ejection fraction (HFrEF) and predominant CSA 1,2 1. Cowie et al. Eur J Heart Fail 2013;15:937-43; 2. Cowie et al. NEJM 2015, 1 Sep [Epub ahead of print].
SERVE-HF: Endpoints Primary composite endpoint: Time first event of all-cause death, life-saving cardiovascular intervention*, or unplanned hospitalization for worsening chronic HF Secondary endpoints: *heart transplant, long-term ventricular assist device, resuscitation of sudden cardiac arrest, or appropriate ICD shock As for primary endpoint, but cardiovascular vs all-cause death As for primary endpoint, but all-cause vs HF-related unplanned hospitalization Time to death (all-cause) Time to cardiovascular death Change in NYHA class Change in 6MWD Quality of life Cowie et al. NEJM 2015, 1 Sep [Epub ahead of print].
Primary Endpoint Neutral Time to first event of all-cause death, life-saving cardiovascular intervention, or unplanned hospitalization for worsening chronic HF Cowie et al. NEJM 2015, 1 Sep [Epub ahead of
Subgroup Analysis: 1 Endpoint Cowie et al. NEJM 2015, 1 Sep [Epub ahead of
All-Cause Death Cowie et al. NEJM 2015, 1 Sep [Epub ahead of
Cardiovascular Death Cowie et al. NEJM 2015, 1 Sep [Epub ahead of
Subgroup Analysis: CV Death Cowie et al. NEJM 2015, 1 Sep [Epub ahead of
Conclusions Addition of ASV to guideline-based medical management does not improve outcomes in patients with HFrEF and CSA despite effective control of CSA These results apply only to the population studied Cannot be generalised to patients with HF with preserved ejection fraction, or those with predominant OSA Cowie et al. NEJM 2015, 1 Sep [Epub ahead of
Hospitalized ADHF subjects (both HFrEF and HFpEF) with moderate/severe SDB (AHI 15, both OSA and CSA) followed for 6 months RCT comparing ASV therapy plus OMT compared to OMT alone Primary Results: Late Breaker HFA May 22 nd, 2016
Estimated Annual Economic Cost of OSA in US Total = $67B 165B Diagnosis and Treatment $2B 10B Loss of Productivity $5B 15B Workplace Accidents $5B 20B Traffic Accidents $10B 40B Hidden Healthcare Costs $45B 80B Source: McKinsey & Company analysis; Harvard Medical School, 2010 Source: McKinsey & Company analysis; Harvard Medical School, 2010
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