Apnea-Hypopnea- Index The new old biomarker for Sleep-Disordered Breathing. Alan S Maisel MD

Transcription

1 Apnea-Hypopnea- Index The new old biomarker for Sleep-Disordered Breathing Alan S Maisel MD

2 Triumvirate of Health-public awareness 1.8% Sleep Physical Fitness Nutrition 91.3% 99.9%

3 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)

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5 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

6 PREVALENCE

7 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

8 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 Logan AL et al. J Hypertens Oldenburg O et al. Eur J Heart Garrigue S et al. Circulation Gami AS et al. Circulation Sjostrom C et al. Thorax Schafer H et al. Cardiology Sanner BM et al. Clin Cardiol

9 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

10 The two-headed patterns of SDB in HF OSA CSA

11 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 % sec Cowie et al. Eur Cardiol Rev 2015.

12 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 % sec Cowie et al. Eur Cardiol Rev 2015.

13 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

14 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

15 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

16 Obstructive Sleep Apnea (OSA) Indicators Habitual loud snoring Witnessed apneas Hypertension Excessive daytime sleepiness Obesity/ neck circumference Morning headaches Heart failure/ CVD

17 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

18 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

19 Patient Video (OSA)

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21 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

22 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:

23 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

24 OUTCOMES

25 AJRCCM 2011

26 Survival SDB in HF Cut off AHI 15/h Bitter et al., Eur Heart J 2010

27 CSA and Mortality in HF Jilek et al., EJHF 2011

28 CSA Predictor Cardiac Readmission Khayat et al., J Cardiac Fail 2012

29 TREATMENT

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31 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

32 Pressure Pressure Pressure PAP Therapy CPAP Time Automatic Positive Airway Pressure (APAP) Therapy Time Bilevel Time

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35 Malhotra et al., NEJM CPC 2003

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37 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

38 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.

39 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.

40 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

41 Bilevel device in CPAP Mode CSR Pattern SpO 2 variable 90-98% Pulse rate variable beats per min

42 Switch from CPAP to ASV mode Respiratory pattern beginning to normalize SpO 2 stabilizing Less variability in pulse rate

43 Respiratory pattern completely normalized SpO 2 stable 94-97% Pulse rate stable beats per min

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45 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].

46 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].

47 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

48 Subgroup Analysis: 1 Endpoint Cowie et al. NEJM 2015, 1 Sep [Epub ahead of

49 All-Cause Death Cowie et al. NEJM 2015, 1 Sep [Epub ahead of

50 Cardiovascular Death Cowie et al. NEJM 2015, 1 Sep [Epub ahead of

51 Subgroup Analysis: CV Death Cowie et al. NEJM 2015, 1 Sep [Epub ahead of

52 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

53 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

54 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

55 SDB s Effect on Cost & Preventable Utilization Schneider CSA patients Trucking Untreated Patients Waste OSA Management w/ heart failure had SA 57.4% patients OSA reduction group averaged 6-month patients CPAP in w/ adjusted total with untreated on PAP medical heart rate therapy failure OSA ratio show OSA of had 37% Improvement treatment 32% reduction resulted inpatient more hospital in in costs total patients admissions 82% medical in 10 with mm higher costs HG improved expenses left than Prior 31% to cardiac ventricular ($6,456/year) diagnosis, less readmission medical ejection OSA costs fraction patients of 1.53 than from reduction HbA1c for those >7 in treated after blood treated treated use pressure, OSA in of patients group 1CPAP which reduces utilized compared 25% Potts et stroke medical patients to to al. risk resources patients 33% by not st year 91% reduction in hospital admissions Hoffman with PAP Health Health 35% Management and 23-50% heart no SDB Potts therapy et al. Journal Kaneko more Khayat et et al. al. Population New by Engl 6.5% of Occupational & Does not J than et control al. Jour Health Med 2003 Card group Fail Management Babu Environmental include savings et al. Arch Medicine, from disease Intern Med vol. by 20% 2005, 52, accidents Harsch. no Berger et al. CHEST Sleep 2004 Becker Smith et al. et Circulation al. Chest

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60 THE HEART OF NATURE Heart River: loc Western North Dakota