Precision Sleep Medicine

Transcription

1 Precision Sleep Medicine Picking Winners Improves Outcomes and Avoids Side-Effects North American Dental Sleep Medicine Conference February 17-18, 2017 Clearwater Beach, FL John E. Remmers, MD

2 Conflict of Interest Part owner of a company that manufactures a sleep recorder (Sagatech) Part owner and Chief Medical Officer of a company that manufactures a dental titration device (Zephyr Sleep Technologies, Calgary, Alberta CANADA) 2

3 Objectives To understand the current balance of patient adherence to therapy versus therapeutic efficacy in outcomes with continuous positive airway pressure (CPAP) and oral appliance therapy (OAT) To be familiar with the role of wakefulness in permitting reflex compensation for the pharyngeal anatomic abnormality To understand the importance of patient selection in the management of OSA with OAT: what methods work and why To learn why mandibular protruding appliances produce a successful outcome in some patients but not others To be familiar with the possible role for emerging technologies in enhancing the accuracy of patient selection for OAT 3

4 Definition of Respiratory Disturbances Apnea absence of breathing for 10 seconds or more Hypopnea 50% reduction in breathing for 10 seconds followed by a 3% dip in O 2 sat or an arousal 4

5 Contraction of Inspiratory Muscles in OSA Negative luminal pressure 5

6 Pathophysiology of OSA: Two possibilities Neural Hypothesis (lazy tongue) Apneics have a sub-normal genioglossal activity during sleep Anatomic Hypothesis (small airway) Apneics have a structurally narrowed pharyngeal airway 6

7 The Passive Pharyngeal Airway General Anesthesia Complete Paralysis 7

8 Closing pressure is elevated in OSA 8

9 Maximal Area of the Passive Pharynx 9

10 Lazy Tongue Hypothesis Tantalizing but fragmentary evidence supports this hypothesis Currently, no hard evidence supports the lazy tongue In fact, the tongue seems to be working overtime while awake 10

11 Genioglossal EMG is elevated in OSA while awake 11

12 Here s the deal - OSA is caused by a structural narrowing of the pharynx This structural narrowing causes airway obstruction ONLY during sleep 12

13 While Awake - Neuromuscular Compensation NO Pharyngeal Obstruction Structural Narrowing 13

14 Non-REM Sleep Pharyngeal Obstruction Structural Narrowing 14

15 REM Sleep - Muscle Atonia Severe Pharyngeal Obstruction Pharyngeal Occlusion 15

16 Oral Appliance Therapy How Does it Work? Studies of the passive pharynx reveal that protruding the mandible acts mechanically to open the pharynx 16

17 Mandibular Protrusion Dilates the Passive Pharynx Note dependence of nasopharynx and oropharynx 17

18 Oral Appliance Therapy How Does it Work? OAT eliminates pharyngeal obstruction in OSA by dilating the velo-pharynx and oro-pharynx No evidence for muscle activation 18

19 Sleep Apnea & Comorbid Disease Depression 45% Stroke 63% Drug-Resistant Hypertension 83% Coronary Artery Disease 57% Heart Failure 76% A-fib 50% Severe Obesity Type 2 Diabetes 77% 72% 19

20 CV Effects Clearly sleep apnea is associated with CV disease Marin JM, Carrizo SJ, Vicente E, Agusti AGN. Long-term cardiovascular outcomes in men with obstructive sleep apnoea-hypopnoea with or without treatment with continuous positive airway pressure: an observational study. Lancet 2005; 365:

21 All Cause Mortality Wisconsin Sleep Cohort Young T; Finn L; Peppard PE; Szklo-Coxe M; Austin D; Nieto FJ; Stubbs R; Hla KM. Sleep disordered breathing and mortality: eighteen-year follow-up of the wisconsin sleep cohort. SLEEP 2008;31(8):

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23 Does CPAP prevent CV disease? 3 recent clinical trials comparing CPAP with usual care Barbe et al. JAMA 2012 Peker et al. Am J Resp Crit Care Med 2016 McEvoy et al. New Eng J Med

24 McEvoy et al. (n=2687) SAVE Trial New Eng J Med 2016; 375: SAVE Trial (Sleep Apnea Cardiovascular Endpoints) 24

25 McEvoy et al. (n=2687) No significant difference in prevention of CV events comparing CPAP vs. controls New Eng J Med 2016; 375: SAVE Trial (Sleep Apnea Cardiovascular Endpoints) 25

26 Conclusions CPAP did not significantly reduce the occurrence of serious CV events in non-sleepy patients with moderate to severe OSA Why not? 26

27 Poor CPAP compliance 3.3 hours per night 27

28 This is why I m so concerned Prescribing CPAP with the sole purpose of reducing future CV events in asymptomatic patients with OSA and established CV disease cannot be recommended Need for novel treatment options Editorial. Mokhlesi B, Ayas N. New Eng J Med 2016; 375(10):

29 YOU have a treatment that will reduce heart attacks and strokes BUT only if you treat the patients who will respond! 29

30 Which ONES? 30

31 Selection Selection Selection 31

32 We need a validated method to prospectively select patients for OAT More efficient delivery of therapy Better outcomes 32

33 Available Methods for Selecting Patients for OAT Clinical features Imaging the pharynx Mandibular titration 33

34 Here s the deal - OSA is caused by a structural narrowing of the pharynx This structural narrowing is not apparent while awake because of neuromuscular compensations 34

35 Available Methods for Selecting Patients for OAT Clinical features Imaging the pharynx Mandibular titration during sleep 35

36 Mandibular Titration During Sleep in the Lab 36

37 MATRx Single-night, Attended Polysomnographic Test 1. Accurately selects patients who will respond to OAT and 2. Identifies an efficacious protrusive position for each responder Remmers J, Charkhandeh S, Grosse J, Topor Z, Brant R, Santosham P, Bruehlmann S. Remotely controlled mandibular protrusion during sleep predicts therapeutic success with oral appliances in patients with obstructive sleep apnea. SLEEP 2013; 36(10):

38 Mandibular Titration During Sleep at Home Replacing the Tech with a Computer 38

39 MATRx plus Home Sleep Test 1. Accurately selects patients who will respond to OAT and 2. Identifies an efficacious protrusive position for each responder Note: This device is approved by Health Canada for sale in Canada. This device is pending 510(k) and 513(f)(2) clearance and is not available for sale in the United States. 39

40 The MATRx plus Difference Every other HST device only supports the diagnosis of OSA MATRx plus does it all 40

41 MATRx plus: A-MP Technology Auto-titrating mandibular positioner MATRx style dental trays Feedback signals: Oxyhemoglobin saturation Respiratory airflow Real-time detection of respiratory events Automated analysis of data 41

42 MATRx plus 42

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45 MATRx plus Patient Information Portal 45

46 MATRx plus Titration: A two night study in the home Night 1 Dynamic interaction between respiratory events and mandibular movement Night 2 Refinement of mandibular position in response to respiratory events 46

47 Protrusive position (mm) MATRx plus Results: Responder Time (h) 47

48 Protrusive position (mm) MATRx plus Results: Non-Responder Time (h) 48

49 Case Study Obese Patient with Severe OSA Patient Profile 62 year old male Pre-study AHI = 40.2 BMI = 34.3 Tray Fitting Lower Limit (Resting Position) - 3.5mm Upper Limit (Maximum Protrusion) + 5.5mm 49

50 Night 1 - Dynamic Theragnostic Study 50

51 Night 2 - Static Theragnostic Study 51

52 Night 3 - Static Theragnostic Study 3.1mm 52

53 Theragnostic Study Summary 53

54 MATRx plus Clinical Investigation Objective To assess the ability of an auto-titrating mandibular positioner test in: Prospectively identifying therapeutic responders Determining an efficacious protrusive position 54

55 MATRx plus Trial Study Design All participants received: 2-night auto-titrating mandibular positioner test Custom oral appliance (SomnoMed G2, MicrO 2 ) 55

56 Inclusion Criteria Broad inclusion criteria: ODI > 10 hr -1 BMI < 45 kg/m 2 56

57 Distribution of Baseline ODI and BMI 57

58 Auto-titration + Machine Learning MATRx plus Machine Learning (Random Forest) Prediction of Outcome with OAT 58

59 Training and Validation of Predictive Model Phase 1: n = 131 Extract 266 feature s Training of Random Forest Machine Therapeutic Outcome Phase 2: n = 48 Extract 266 feature s Trained Random Forest Machine Responder or Non- Responder 59

60 Baseline and Outcome ODI n=48 60

61 Predictive Accuracy: Patient Selection Therapeutic success defined as ODI < 10hr -1 61

62 Efficacious Protrusion (%) Predictive Accuracy: Efficacious Protrusive Position PPV=86% Target Protrusion (%) 62

63 Why does MATRx work so well? Test Prediction Outcome Test circumstances mimic the outcome situation 63

64 Efficiency: Fewer Clinic Visits 64

65 Efficiency: Reduced Time-to-Treatment Days from OA Insertion to Therapeutic Success Prediction Mean±SD Range Predicted Success 29.3± Predicted Failure 76.9±

66 Conclusions CPAP is still standard treatment for OSA but it has clay feet OAT is great treatment for OSA BUT it must incorporate patient selection The at-home sleep test, MATRx plus, provides accurate patient selection for OAT 66

67 MATRx plus Empowering the Sleep Dentist Know, in advance, OSA patients who will be effectively treated with an oral appliance Improve your efficiency of appliance fitting at target Decrease the time-to-therapy Minimize the risk of over-titration 67

68 Acknowledgements National Research Council Canada Industrial Research Assistance Program Alberta Innovates Technology Futures SomnoMed MicroDental Laboratories Zephyr Sleep Technologies 68