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NovelWaysofDiagnosingSleep-DisorderedBreathing

KobySheffy,PhDBoston2017

Disclosure

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IamtheChiefScientistandSr VPatItamar Medicalandaco-inventorofPAT

Nothingelsetodisclose

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anythingnewunderthePicturesque Sun Guys?

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SDB was Defined by PSG – it is a Synergy “Polygraphic StudyoftheEpisodicDiurnalandNocturnal(hypnicandrespiratory)ManifestationsofthePickwickian Syndrome.” Gastaut H etal,BrainRes. 1965;2:167–86.

And10yearslatercomprehensivelyestablished:

"Thesleepapneasyndromes". Guilleminault,C;Tilkian,A;Dement,WC.AnnualReviewofMedicine1976; 27:465–484.

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Dr.Gastaut Dr.Dement Dr.Guilleminault

Emerging innovations over the years

¡ ChallengingthewellestablishedPSG¡ Thevenue(takingithome)¡ Thetechnology(fromanalogpaperrecordertodigitalPCand

more)¡ Thephysiologicalchannelsandinterpretations

¡ Startedasearlyasthe80’s

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Driven by

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Hardtosleepthere

Hardtogetthere

Hardtopayit

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`Thinking out of the PSG Box – the 80’s

¡ Somenewinnovations¡ Takingithome¡ Newtechnologies¡ Newinterpretations

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ChapeauDr.Penzel !!!

The 4 Diagnostic Levels Approach

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Penzel TandPeterJH,SleepandHealthRisks1990

inductiveplethysmography2belts,partialoxygenpressureusingSeveringhauselectrodes,ECG,4channelaudiotapeatslowspeed,infraredLEDequippedglassesforvigilancemonitoring.

TheMarburgKofer - 1982

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Vitalog HMS-300 “Lunchbox” – 1990

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MilesLE,1990

Messam - 1988

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Messam 4 - 1990

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What can you do on bed in a long cold Finish night

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What can you do on a cold Finish night in bed ?

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Countelks

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What can you do on a cold Finish night in bed ?

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Makelove

What can you do on a cold Finish night in bed ?

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Orthink

What can you do on a cold Finish night in bed ?

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Andthenrealize– inFinlanditallhappensonthemattress

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The Static Charge Sensitive Bed

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ALIHANKAJetal,EEGClinNeurology1978

The Static Charge Sensitive Bed

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ALIHANKAJetal,EEGClinNeurology1978 Kirvajainen Tetal,JSleepRes1995

Taking it Home – the 90’s

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Theestablishmentoftheambulatorycardio-pulmonarysleepdevices(NAF,RespiratoryBelts,ECG,SaO2)

Remmers - bedsideEdenTech - bedsideSynectics - bedsideEmbleta - wearableStardust- wearable……….……..

Gainingsimplicity/costCompromisingon• TST(AHIbyTRC)• Sleepstages(effectonsleep,REMrelatedOSA)

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Challenging the at Home Limitations – the 21 Century

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EEG/EOG(frontalelectrodes)NAFSnoringSpO2HeadMovement

ARES– theApneaRiskEvaluationSystem

WestbrookPRetal,Descriptionandvalidationoftheapneariskevaluationsystem:anovelmethodtodiagnosesleepapnea-hypopneainthehome.CHEST2005

Dr.PhilipWestbrook

Disclosure

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IamtheChiefScientistandSr VPatItamar Medicalandaco-inventorofPAT

Nothingelsetodisclose

The PAT Signal and Technology

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SchnallRP,Shlitner A,SheffyJ,Kedar R,&Lavie P.Periodic,ProfoundPeripheralVasoconstriction– ANewMarkerofobstructiveSleepApnea.SLEEP1999;

“….. GiventhatelevatedperipheralresistanceandtightlylinkedtransientheartrateelevationisaconsistentpartofthehemodynamicresponsetoarousalandOSAS,webelievethatpulsatilefingerbloodflowpatternscanbeclearlydiagnosticofOSAS andothersleep-disorderedbreathingconditions.”

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PAT® Signal - pulsatilearterialvolumeattheFingerTip

The PAT® (Peripheral Arterial Tone) Signal

Reflectsvasomotortoneatthefingertip

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Awindowtotwovaso-regulatingsystems:

Thearterialendothelialsystem

Theautonomicnervoussystem– sympatheticbranch

A Window to the Autonomic Nervous System

Autonomic N.S Sensor-Motor N.S.

Sympathetic N.S.

“Stress response” Para-Sympathetic N.S.

a receptors b receptors

Vasoconstriction VasodilatationPeripheral Artery:

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PAT (finger) and forearm blood flow response to non-selective α-adrenergic agonist

1215151515 1215151515N =

norepinephrine (pmol/100ml/min)

1,420472120317.4

% ch

ange

in flo

w / P

WA

20

0

-20

-40

-60

-80

-100

fingerplethys-

mography

forearm flow

measurement

n=12

Zou D, Grote L, Eder DN, Peker Y, Hedner J. SLEEP 2004, 27:485-9.27

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PAT (finger) and forearm blood flow response to a selective b-adrenergic agonist

13131414 13131213N =

isoproterenol (ng/100 ml/min)

15621

% ch

ange

in flo

w / P

WA

300

200

100

0

-100

fingerplethys-

mography

forearm flow

measurement

n=12

Zou D, Grote L, Eder DN, Peker Y, Hedner J. SLEEP 2004, 27:485-9.28

Association of PAT and Sympathetic Marker at the End of Each Apnea Episode

EOG

ECG

EMG

RESP

Thorax

DB

PAT

Blood Pressure

EMGSaO2

CourtesyofProf.ThomasPenzel

PSG

PSG

Apneaepisode

Movementnoise

Oxygendesaturation

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WatchPAT

PATProbe

BodyPosition&SnoreSensor

WatchPATUnified

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TakingittothePatientHome

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…..andItsFeatures

•Automaticanalysis• manualeditingavailable

•ClinicalApplications:• AHI(ApneaHypopneaindex)

•(Apneas+Hypopneas)/totalsleeptime• RDI(RespiratoryDisturbanceIndex)

•(Apneas+Hypopneas+RERAs)/totalsleeptime• ODI(Oxygendesaturationindex)• Wake/Sleepdetection• REM/Deep/Lightsleepstages• Snoring• BodyPosition

•ComprehensiveReport

•Comfortable- minimalsleepinterference

WatchPAT® Screen – Identified Respiratory Events (Sleep Apnea)

PATAmplitude:Decrease

PulseRate:Increase

Oxygen:Desaturation

Actigraph:Movement

Snoring :Surge

Position:Supine

PATSignal:Attenuation

Respiratory eventchannels change

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Differentiating beteen Sleep and Wake

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• A3Daccelerometerbasedactigraphy• Alearningmachinepahse ofthe

backgroundmovements(energy)• PAT/Oxi sleeppatterns

Multicenter sleep/wake novel algorithm validation

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SLEEP2004:27(8):1560-6

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1. Step1findsleep/wake(FirstwetakeManhattan..….)

1. Step2findREM/NREM(andthenwetakeBerlin…….)

1. Step3differentiatebetweenDeepandLightsleepintheNREMepochs(andmaybethenBoston…)

WatchPAT® identificationofSleepStages

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WatchPAT REM/Deep/light algorithm description

¡ Differentialactivation(sympatheticvs.parasympathetic)insleepstages– subcorticalmanifestation

¡ 16featuresextractedfromthePATsignal

¡ Time andfrequencydomainanalysisofevents– providesakindofsympatheticsignature

¡ Afewfeaturescanbeeyeballed

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EOG

PAT

15 min

A

Motion artifact

PAT in REM sleep

Lavie P,SchnallR,SheffyK,Shlitner ANatureMedicine6:606,2000

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WatchPAT® identifies sleep stages

Lightsleep:highPATamplitudevariability,high

pulseratevariability

Deepsleep:lowPATamplitudevariability,low

pulseratevariability

REMsleep:veryhighPATamplitudevariability,veryhighpulseratevariability,attenuatedPATamplitude

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SleepstagesonWatchPAT®reportvs.PSG-EEGchannel

WatchPAT® identifies sleep stages

Lightsleep:highPATamplitudevariability,high

pulseratevariability

Deepsleep: lowPATamplitudevariability,lowpulseratevariability

REMsleep:veryhighPATamplitudevariability,veryhighpulseratevariability,attenuatedPATamplitude

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SleepstagesonWatchPAT®reportvs.PSG-EEGchannel

WatchPAT® identifies sleep stages

Lightsleep:highPATamplitudevariability,high

pulseratevariability

Deepsleep: lowPATamplitudevariability,lowpulseratevariability

REMsleep: veryhighPATamplitudevariability,veryhighpulseratevariability,attenuatedPATamplitude

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SleepstagesonWatchPAT®reportvs.PSG-EEGchannel

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MetaAnalysesWatchPAT® vs.PSG(cont.)

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1. Hedner JPillarG,PittmanS,Zou D,Grotte L,WhiteD.ANoveladaptivewristactigraphy algorithmforSleep-Wake assessmentinsleepapneapatients.SLEEP2004;27(8):1560-1566.

2. Herscovici S, Pe'er A, Papyan S, Lavie P .DetectingREMsleepfromthefinger:automatic REMsleepalgorithmbasedonPeripheralArterialTone(PAT)andactigraphy.Physiol Meas 2007;28(2):129-140.

3. BreslerM,Sheffy K, Pillar G, Preiszler M, Herscovici S .DifferentiatingbetweenlightanddeepsleepstagesusinganAmbulatoryDeviceBasedonPeripheralArterialTonometry. Physiol Meas.2008;29(5):571-584.

4. Hedner White DP, Malhotra A, Herscovici S, Pittman SD, Zou D, Grote L, Pillar G.Sleepstagingbasedonautonomicsignals:amulticentervalidationstudy.JClin SleepMed2011;7:301-306.

Overallsleepstagesagreementinthe70-80%range

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Sleep Stages Validation Papers:

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Central vs. Obstructive Sleep Apnea Differentiation –a New WatchPAT capability

• PAT signal upstroke variations

• Respiratory movements(from SBP accelerometer)

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T Penzel 1, D Hwang4, A Rama3, P Manthena 4,5, R Berry6, R Spiegel7, M Berall8, MaraiIbrahim9, Y Henkin10 , R Tauman11 , G Pillar2

,APSS2016

obstructive

central

Post Modernism Era

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“Thisworkcanbeconceivedofaspostmoderninmanysenses:itsovertreferencetopopularculture/lowartchallengesthepurityofthemodernistaesthetic,itsrepetitiveelementisanhomagetomassproduction…..”fromtheCatalogue,TateModern,London

MarilynDiptych,AndyWarhal

The Healthcare Post Modernism – the contemporary era

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Creatingpostmodernhealthcare

Peoplemodernise healthcareinanattempttoabsorbtheeffectofrisingneedanddemandresultingfromdemographic,technical,andsocialchanges thatlieinthepathofeveryhealth-caresystem.Tocope,postmodernhealthwillnotonlyhavetoretain,andimprove,theachievementsofthemodernera,butalsorespondtotheprioritiesofpostmodernsociety—namely:concernaboutthevaluesaswellasevidence;preoccupationwithriskratherthanbenefit;theriseofthewell-informedpatient.

MuirGrayJA,THELANCET•Vol354•October30,1999

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Contemporary innovations – the Smartphone era

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10ThingsYouDidn’tKnowYouCanDowithYourSmartphoneby ElizabethHarper on September08,2016in PhoneAccessories, PhonesandMobile,MobileApps, Tips&How-Tos

DiagnosealeakywindowMeasureyourhearthealthPreventdrunkdrivingSeeeverythingupcloseMeasureyourmusclesFigureoutwhyyourcheckenginelightisonRemindyoutodrinkenoughwaterDosomemath(withoutacalculator)ImproveyourbasketballskillsCatchafish

DefinitelydiagnosesleepingeneralandSDBinparticular

Fietze , Sleep Medicine Clinics 11: 461-468 (2016)

Android applications by Google Store. Accessed July 8, 2016Free to 10 Euro

SleepApps Search in Google

Smartphone Applications

Motion sensingMicrophone More sensors Grifantini K. IEEE Pulse Magazine, Sept. 2014

Sleepcycle to Wake

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VitalPatch – small and disposable

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Somnarus Patch

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AirflowHeartrateRespiratoryeffortBloodoxygenBodypositionSleep

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Ballistocardiography- (BCG)isameasureof ballisticforcesontheheartgeneratedbytheejectionofbloodintothebigvesselsbyeachheartbeat.Emfit – Electromechanicalfilmtransducer

Sleepmonitoringanalyzedbyheartratevariability.Allparametersmeasuredbyasensorunderthemattress,includingheartrate,breathingrate,movementactivityandallsleepclasses.

Emfit QS

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Beddit – taking the Smart Sheet to the Smartphone

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Beddit – As from May an Apple product

Paalasmaa J, Toivonen H, Partinen M: Adaptive Heartbeat Modeling for Beat-to-Beat Heart Rate Measurement in BallistocardiogramsIEEE JBHI 19:1945-1952 (2015)

The Sonomat – vibration & acoustic sensors

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Dr.ColinSullivan

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BresoDx – Acoustic and Movement

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Dr.DougBradley

Alshaer Hetal,Sleepmedicine2016

ResMed behind - S+

¡ TheS+measuresmovementsusingultralowpowerradiowaves

¡ noncontactsensingofrespirationpattern

¡ reportsREMandNREMsleepstagesbasedonstage-specificbreathingpatterns

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¡ Nonmedicalgrade- andyetResMed ……

Nokia behind - Withings Aura Sleep System

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LightwavesAcousticWavesSleepandrespirationanalysis

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ApneaApp

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AcollaborationbetweenUWandOxford

The Zeo adventure

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Features:• NewEEG/EOGelectrodestechnology• Sophisticatedneuralnetworkexpertsystem• Sleepquality• Self-trainingusingartificialintelligence

The Zeo adventure

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• Thehottestnamesinsleepresearch

• Thehottestnamesinbio-medicalbusiness

• Investigatorswerequeuing

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Consumer sleep monitors: is there a baby in the bathwater? K Russo et al, Nat Sci Sleep 2015

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Therapidexpansionofconsumersleepdevicesisoutpacingthevalidationdatanecessarytoassessthepotentialuseofthesedevicesinclinicalandresearchsettings

Toplacethemarketingtrendsandconsumerdemandintoperspective,wenotethataconsumersleepmonitorwithnopublishedvalidation waslistedamongTimeMagazine’sinventionsoftheyearin2005

Themorewidelytheseproductsenjoyconsumption,themoreurgentlyimportantitisforallstakeholderstoengageinresolvingthecurrentstateofclaimvalidationmismatch

So where does it take us? Up or Down?

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Opportunities

Newexcitingtechnologies

Involvementof“supperpowers”–resources

Consumermarket–expandawarenesstosleep

Risks

Lackofpivotalvalidation

Involvementof“Supperpowers”– biasofeconomicalinterest

Consumermarket–consumerscontrolofmedcal procedures

Up or Down?

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InotherwordsOptimistic?Pessimistic?

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Probably something in between

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TheOpsimistic….EmileHabibi,1984

Many Thanks to Colleagues

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Dr.BobSchnallDr.Peretz lavie LateDr.DanielGoor