Health-related quality of life after surviving an out-of-hospital compared to an in-hospital cardiac arrest: A Swedish population-based registry study

Clinical

paper

Health-related

quality

of

life

after

surviving

an

out-of-hospital

compared

to

an

in-hospital

cardiac

arrest:

A

Swedish

population-based

registry

study

Therese

Dja¨rv

*

,

Anders

Bremer

,

Johan

Herlitz

,

Johan

Israelsson

,

Tobias

Cronberg

,

Gisela

Lilja

,

Araz

Rawshani

,

Kristofer

A˚restedt

a_{KarolinskaInstitutet,Stockholm,Sweden}

b_{LinnaeusUniversity,FacultyofHealthandLifeSciences,Kalmar/Va¨xjo¨,Sweden} c

GothenburgUniversity,DepartmentofMolecularandClinicalMedicine,Gothenburg,Sweden

d

DepartmentofInternalMedicine,DivisionofCardiology,RegionKalmarCounty,Kalmar,Sweden

e_{DepartmentofMedicalandHealthSciences,DivisionofNursingScience,Linko¨pingUniversity,Linko¨ping,Sweden} f_{LundUniversity,SkaneUniversityHospital,DepartmentofClinicalSciencesLund,Neurology,Lund,Sweden} g_{ClinicalPhysiology,SahlgrenskaUniversityHospital,Gothenburg,Sweden}

h

TheResearchSection,RegionKalmarCounty,Kalmar,Sweden

Abstract

Background:Health-relatedqualityoflife(HRQoL)hasbeenreportedforout-hospital(OHCA)andin-hospitalcardiacarrest(IHCA)separately,but potentialdifferencesbetweenthetwogroupsareunknown.TheaimofthisstudyisthereforetodescribeandcompareHRQoLinpatientssurviving

OHCAandIHCA.

Methods:Patients18yearswithCerebralPerformanceCategory1 3includedintheSwedishRegistryforCardiopulmonaryResuscitationbetween 2014and2017wereincluded.Atelephoneinterviewwasperformedbasedonaquestionnairesent3 6monthspostcardiacarrest,includingEQ-5D-5L andtheHospitalAnxietyandDepressionScale.Mann WhitneyUtestandmultiplelinear-andordinallogisticregressionanalyseswereusedto describeandcompareHRQoLinOHCAandIHCAsurvivors.Adjustmentsweremadeforsex,ageandinitialrhythm.

Results:Inall,1369IHCAand772OHCAsurvivorswereincluded.MostOHCAandIHCAsurvivorsreportednosymptomsofwithanxiety(88%and 84%)ordepression(87%and85%).IHCAsurvivorsreportedsignificantlymoreproblemsinthehealthdomainsmobility,self-care,usualactivitiesand pain/discomfort(p<0.001forall)andscoredlowergeneralhealthmeasuredbyEQ-VAS(median70vs.80respectively,p<0.001)comparedwiththe OHCAsurvivors.

Conclusion:SurvivorsofIHCAreportedsignificantlyworseHRQoLcomparedtosurvivorsofOHCA.Consequently,researchdatagatheredfromone ofthesepopulationsmaynotbegeneralizabletotheother.

Keywords:Health,Heartarrest,Psychologicaldistress,Qualityoflife

Abbreviations:IHCA,in-hospitalcardiacarrest;OHCA,out-of-hospitalcardiacarrest;CPR,cardiopulmonaryresuscitation;VT,ventricletachycardia; VF,ventriclefibrillation;PEA,pulselesselectricactivity;HRQoL,health-relatedqualityoflife.

* Correspondingauthor.

E-mailaddress:therese.djarv@ki.se(T.Djärv).

https://doi.org/10.1016/j.resuscitation.2020.04.002

Received3February2020;Receivedinrevisedform29March2020;Accepted2April2020

0300-9572/©2020TheAuthor(s).PublishedbyElsevierB.V.ThisisanopenaccessarticleundertheCCBYlicense(http://creativecommons.org/licenses/ by/4.0/).

Available

online

at

www.sciencedirect.com

Resuscitation

Introduction

Outcomefollowingcardiacarresthasprimarilybeenreportedinterms ofmortality or withcrude functional outcomescales such asthe

Cerebral Performance Category (CPC) scale. However, other

outcomes such ashealth-related qualityof life (HRQoL) maybe more relevant from the patient perspective.1 _{Furthermore, the}

InternationalLiaisonCommitteeonResuscitationandtheCOSCA (CoreOutcomeSetforCardiacArrest)grouphaverecommended HRQoLas acore outcomein cardiacarresttrials.2,3 Inprevious studiesincludingHRQoLmeasures,mostsurvivorshavereporteda good HRQoL.4,5 _{Nevertheless, cognitive, emotional and physical}

problemsarecommonandrestrictsthesurvivor'slifeandabilityto participateinsocietalactivities.6,7

Whetheracardiacarrestoccursoutsideorwithinahospitalhasa fundamentalimpactonsurvival,i.e.nationaloverallsurvivalratesin Swedenare35%forIHCAand10%forOHCA.8,9_{Exceptforbetter}

survival,IHCAsurvivorsareingeneralolderandthetimebetweenthe arrestanddefibrillationismuchshorter.10Boththesefactorsmaybeof significantimportanceforHRQoLbutfewstudieshavecomparedthe

two groups. Individual studies on IHCA and OHCA survivors

respectivelyhaveconcluded thatHRQoLingeneralaregoodand comparable to general populations.4,5,11 _{Lack of consistence in}

design,timeforfollow-upandmeasuresmakeitdifficulttodrawany strongconclusionsaboutdifferencesinHRQoLbetweenIHCAand OHCAsurvivors.However,somedifferenceshavebeen demonstrat-edintwoofthelargestHRQoLstudiesincardiacarrestsurvivors madesofarbySmithetal.5_{(OHCA)andIsraelssonetal.}4_(IHCA).

BasedonEQ-5D,thesestudiesconcludethatpainisacommonhealth problem.However,Smithetal.5reportedproblemswithself-careas mostcommonandanxietyanddepressionaslesscommoninOHCA survivors.Israelssonetal.4_{reportedtheopposite,exceptforpain,}

problems with anxiety and depression were most commonwhile problems with self-care were least common in IHCA survivors. However, both studies have different follow-up time and was conductedin twocountrieswithdifferenthealthcaresystems. To improvepostcardiacarrestcare,itisofimportancetoextendthe knowledgeaboutHRQoLinIHCAandOHCA.Therefore,theaimwas todescribeandcompareHRQoLinpatientssurvivingOHCAand IHCAinanationwidepopulation-basedstudy.

Methods

Studydesignandsettings

Thisregistry-basedstudywasconductedinSwedenfrom1stJanuary 2014to31stDecember2017.Nearly100%ofallpatientssuffering fromOHCAandwhereresuscitationwasattemptedareincludedinthe web-based Swedish Register of Cardiopulmonary Resuscitation. Similarly,95%(n=73)ofallhospitalswithintrahospitalresuscitation teamsreportedIHCAtotheregistry.Inclusioncriteriafortheregistry areaccordingtoUtsteinguidelinesanddefinedas“ahospitalised patient who is unresponsive with apnoea (or agonal, gasping respiration) where CPR and/or defibrillation has been initiated.” PatientsarecategorizedasOHCAiftheeventhastakenplaceoutside hospitalandIHCAiftheeventoccurredwhilethepatientwaswithinthe walls of a hospital. The Swedish Register of Cardiopulmonary ResuscitationislinkedtotheSwedishTotalPopulationRegistry,held

bytheNationalBoardofHealthandWelfare,fromwhichvitalstatus dataareautomaticallyretrievedandupdatedseveraltimesperweek. This allows for complete follow-up for survival status of all participants.12Dataisenteredintotheregistryonthreeoccasions, similarlyforOHCAandIHCA.Thefirstandsecondregistrationoccurs incloseproximitytothecardiacarrestandincludesdataonpatient characteristics(e.g.,ageandsex),cardiacarrestcharacteristicsand treatments,postresuscitationcare,survivalandCPC-score.Starting in August2013 athird registration is performed on survivorssix months(timewindowthreemonths)afterresuscitation,including HRQoLassessments.Thepresentstudyismainlybasedonthisthird registration.

Procedureandparticipants

Allsurvivors,18yearsorolder,aliveatthreemonthsaftertheircardiac arrestweremanuallyscreenedforeligibilitytoparticipateinHRQoL assessments by registry nurses. Criteria for exclusion were: unwillingnesstoparticipate,severecognitivedysfunction,language difficulties, and severe physical and/or psychological difficulties (accordingtothelatestmedicalfile).However,survivorswithsevere cognitivedisabilitycouldbeincludedifPROXYraters,e.g.,aspouse, couldbeidentified.Theremainingpatientsweresentaninvitation letterandaquestionnaireincludingtheEQ-5D-5LandtheHospital AnxietyandDepressionScale(HADS)totheirhomeaddress.The letterincludesinformationabouttheregistryandaninvitationtoa telephonefollow-up interviewwheretheir responses tothe ques-tionnaireswerecollected.Thefollow-upinterviewswereperformedby resuscitationcoordinatorsorcardiacrehabilitationnursesdepending onhospitalorganization.Inaddition,ascoringofcerebralfunction according to CPC is conducted based on information from the conversationand/orpatientrecords.

Measuresofhealth-relatedqualityoflife Generichealthstatus(EQ-5D-5L)

TheEQ-5D-5Lisagenericmeasureofself-reportedhealthstatusand consistsoffivehealth-dimensions:mobility,self-care,usualactivities, pain/discomfort and anxiety/depression. Each dimension has five responseoptions,fromnoproblems(1),toextremeproblems(5).The EQ-5D-5Lalsoincludesaseparatemeasureofgeneralhealth,calledthe EQVAS,wheretherespondentsratetheirownperceptionoftheircurrent healthonaverticalscalefrom“theworsthealthyoucanimagine”(0)to “thebesthealthyoucanimagine”(100).TheEQ-5D-5Lhasshowngood measurement properties in termsof validity and reliability and has previouslybeenusedincardiacarrestpopulations.7,13_{Inaddition,itis}

recommendedintheCOSCAadvisorystatement.2

HospitalAnxietyandDepressionScale

TheHADSisasymptomspecificmeasuredevelopedtodetectsymptoms ofanxietyand depression.14 _{Itconsistsof14items, ofwhich seven}

correlateswithanxietyandsevencorrelateswithdepression.Eachitem hasfourresponsecategories,from0to3.Theresponsesfortheitems withineachdomainaresummed,withapossiblescorerangebetween0 and21foranxietyanddepressionrespectively.Higherscoresindicate moreseveresymptomsofanxietyand/ordepression.Differentcut-off levelshavebeensuggested.15_{Inthepresentstudythefollowingwere}

used: normal (0 7), mild (8 10), moderate (11 14), and severe (15 21).16TheHADS has showngoodmeasurement propertiesfor medicalpatients17_{andhasbeenusedincardiacarrestresearch.}4,7

Statisticalanalyses

Univariate statistics were used to describe the characteristics of patientsandstudyvariables.Totestforgroupdifferences,Pearson chi-squaretestorMann WhitneyUtestwereconducted,basedon typeanddistributionofdata.TocompareHRQoLbetweenOHCAand IHCAsurvivors,Personchi-squaretestwereusedfornominaldata andMann WhitneyUtestforordinaldata.Regressionanalyseswere conducted to control forage and sexdifferences. Multiple linear regressionwasusedwhenEQVASandHADSsubscalescoreswere usedasoutcomevariables. Tohandletheordinalnatureofdata,

multiple generalized logistic regression for ordinal dependent variables(unconstrainedproportionaloddsmodel)wasusedwhen EQ-5D health dimensions were the outcome variables. In all regression models,type of cardiacarrest(OHCAvs. IHCA) was usedastheexplanatoryvariablewhileage,sexandinitialrhythmwere included asadjusting covariates. Initialrhythm was grouped into shockable (VTand VF),non-shockable (asystoleand PEA)and “unknown”,andthenenteredintothemodelsasdummyvariableswith shockable rhythm as reference category. The level of statistical significancewassetatp<0.05.Allanalyseswereperformedwith Stata16.0forWindows(StataCorpLLC,CollegeStation,TX,USA).

Table1–Characteristicsof2141Swedishpatientssurviving6monthsaftercardiacarrestduring2014 2017.

OHCA,n=772 IHCA,n=1369 p-valuea

Sex,n(%)

Men 599(77.6) 888(64.9) <0.001 Age(years),Mean(SD) 63(14) 69(13) <0.001 Agecategory,n(%) <0.001 18 30 22(2.9) 18(1.3) 31 40 34(4.4) 16(1.2) 41 50 80(10.4) 92(6.7) 51 60 160(20.7) 195(14.3) 61 70 237(30.7) 377(27.6) 71-80 169(21.9) 439(32.1) >80 70(9.1) 208(16.9) Co-morbidities,n(%) NA Diabetes 313(22.8)

Previousmyocardial infarction 318(23.2)

Cancer 176(12.8)

Placeofcardiacarrest,n(%) NA Home 325(42.1)

Publicplace 276(35.8)

Patientward 310(22.6) Cardiacward/HighDependencyUnit 316(23.1) Intensivecareunit 131(9.5) Operating/procedurerooms 105(7.7) Angiocathlab 281(20.5) EmergencyDepartment 182(13.2) Others 171(22.2) 34(2.5)

Witnessedcardiacarrest,n(%) <0.001 Yes 692(89.6) 1282(93.6)

Missing 6(<1) 19(1.4)

BystanderCPR,n(%) NA

Yes 399(51.7)

Initialdocumentedheartrhythm,n(%) <0.001 VT/VF 563(72.9) 717(52.4) PEA 45(5.8) 130(9.5) Asystole 44(5.7) 284(20.7) Missing 123(15.9) 238(17.4) Presumedetiology,n(%) <0.001 Cardiac 597(77.3) 914(66.8)

Hypothermia/targettemperaturemanagement,n(%) <0.001 Yes 13(1.6) 79(5.8)

CerebralPerformanceCategoryatdischarge,n(%) 0.19 1 568(73.6) 989(72.2)

2 105(13.6) 132(9.6)

3 30(3.9) 47(3.4)

4 5 5(<1) 5(<1) Missing 60(7.8) 175(12.8)

Ethics

Allsurvivorsare informedper mailabouttheirparticipationin the SwedishRegisterofCardiopulmonaryResuscitationandcanatany timewithdrawtheirconsenttoparticipateintheregistry.Sincethestart oftheregistryin1990onlyahandfulofpatientshavewithdrawntheir participation.ThisstudywasapprovedbytheRegionalEthicalReview BoardinStockholm,Sweden,No.2013/1959-31/4.

Results

Patientcharacteristics

Inall,772OHCAsurvivorsand1,369IHCAsurvivorsinSwedenduring 2014 2017wereincluded.Theresponserateswere55%(772outof 1415 survivors) for OHCA survivors and 57% (1369 outof 2384 survivors)forIHCAsurvivorsintheSwedishRegisterof Cardiopulmo-naryResuscitation.Reasonstonotparticipatewereasfollowingfor OHCA(n=643)andIHCA(n=1015)respectively:Unknown277(43%) and531(52%),otherreason184(29%)and245(24%),unwillingness toparticipate68(11%)and92(9%),severecognitivedysfunction46 (7%)and77(8%),languagedifficulties14(2%)and49(5%),deceased betweeninclusionandresponses54(8%)and21(2%).

TheproportionofmaleswashigheramongOHCAsurvivorsthan among IHCA survivors (78% and 65%, respectively, p<0.001). SurvivorsofOHCAwereingeneral5yearsyoungerthansurvivorsof IHCA(p<0.001).Thus,18%ofOHCAsurvivorswereyoungerthan 51yearscomparedto9%ofIHCAsurvivorsand9%oftheOHCA survivors were atleast 81 years old compared to 17% of IHCA survivors.Regardless thelocationfortheCA,mostsurvivorshad suffered awitnessed cardiacarrest(90% OHCA vs. 94% IHCA, p<0.001)andhadashockablerecordedinitialrhythm(73%OHCA

vs.52%IHCA,p<0.001).Atdischarge,threequartersofthesurvivors hadCPC1,74%forOHCAand72%forIHCA(Table1).

Generichealthstatus(EQ-5D-5L)

The IHCA survivors reported significantly worse health status

measured byEQVAScomparedtotheOHCAsurvivors(median

(IQR);70 (50 80)vs. 80(65 90), p_<0.001).Survivorsof IHCA reportedasignificantlyhigherprevalenceofproblemswithmobility (49%vs.29%,p<0.001),self-care(24%vs.13%,p<0.001),usual activities(52% vs.41%,p<0.001),and pain/discomfort(61%vs. 53%, p<0.001)comparedwithsurvivorsofOHCA.Nosignificant differencesinprevalencewasdetectedforanxiety/depression(49% vs. 47%, p=0.28) (Fig. 1). Thesurvivors of IHCA also reported significantlyhigher meanscores,i.e.more healthproblems, inall dimensions (p<0.001)except for anxiety/depression(p=0.24) of EQ-5D-5L (Fig. 2). The regression analyses showed that the differencesinhealthstatusremainedafteradjustmentforage,sex andinitialrhythm(Tables2and3).

Anxietyanddepression(HADS)

Accordingtothecut-offlevels,thevastmajorityofsurvivorsofboth OHCAandIHCAreportednormallevelsofsymptomsofanxiety(88% vs.84%,p=0.03)anddepression(87%vs.85%,p=0.23).Basedon theHADSsubscalescores,theIHCAsurvivorsreportedsignificantly higherlevelsofsymptomseverityinanxiety(median(IQR);OHCA2 (0 5)vs.IHCA2(0 6),p=0.004)anddepression(median(IQR); OHCA2(0 4)vs.IHCA2(1 5),p<0.001)comparedwithOHCA survivors(Fig.3).Theregressionanalysesshowedthatthedifference insymptomseverityofanxietyremainedafteradjustmentforage,sex andinitialrhythm.Incontrast,nodifferenceremainedinsymptom severityofdepressionintheadjustedregressionmodels(Table3).

Fig.1–DistributionofanswersinthedomainsofEQ-5D-5L6monthsafteracardiacarrestinSwedenduring2014

2017,separatedforout-of-hospital cardiacarrest(OHCA)andin-hospital cardiacarrest(IHCA). Alldifferences

Discussion

Thisnationalpopulation-basedHRQoLstudyis,sofar,thelargest amongcardiacarrestsurvivorsandthefirstthatcomparesHRQoL betweenOHCAandIHCAsurvivors.Theresultsshowthatsurvivorsin generalreportedgoodHRQoLbutwithgreatindividualvariations. Moreover, OHCA survivors reported significantly better HRQoL comparedtoIHCAsurvivors.

In consistence with previous researchin CA,7 we found that survivors in generalreported goodHRQoL. A previous study by Israelssonetal.,11_{withbothIHCAandOHCAsurvivors,showedthat}

differences inHRQoLbetween survivorsandan ageandgender matchedgeneralpopulationwassmallandthatthesurvivorsinsome measuresreportedbetterHRQoLcomparetothegeneralpopulation. Basedon thesefindings,poorHRQoLseemsnottobeageneral problemforcardiacarrestsurvivors.However,an importantresult fromthepresentstudyisthelargevariationinHRQoLamongthe survivorsregardlesswhetherittookplacein-oroutsidehospital.Thus, it is important to identify survivors at risk for poor HRQoL. ImplementingassessmentsofHRQoLinpostcardiacarrest follow-upcaremightconstitutemeanstoscreenforthoseinneedofsupport. Insuchacontext,patientsalsoreportingmildtosevereproblemswith anxietyanddepression atHADS oranyother measuremightbe identifiedandreceiveappropriatetreatment.Inordertobetteridentify survivorsatriskofpoorHRQoL,longitudinalstudiessearchingfor predictorvariablesarerequired.

OurmainfindingisthatIHCAsurvivorsreportedsignificantlylower HRQoLcomparedtosurvivorsofOHCA(exceptforsymptomsof depression).Although no previous studyhave compared HRQoL betweenOHCAandIHCAsurvivorsatthesametimeandwiththe samemeasures,thisfindingareconsistentwithlargecardiacarrest studiesbySmithetal.5_{andIsraelssonetal.,}4_{whichbothusedEQ}

VASasameasureofHRQoL.ThesestudiesshowedthatOHCA

survivorshadamedianscoreof75inEQVAS5_{comparedto70in}

IHCAsurvivors.4_{ItisreasonabletoassumethatIHCAsurvivorssuffer}

from more extensive comorbidity than OHCAsurvivors sincethe formergroupisolder,whichmayexplainthisdifferenceinHRQoL betweenthetwogroups.Moreover,patientswhosufferfromanIHCA arehospitalizedforareason,i.e.adiseasethatmayhaveasynergistic negativeimpactonHRQoLincontrasttosufferingfromandsurviving anOHCAwithoutanyadditionalco-morbidities.Co-morbiditymight alsoresultinalongertimethansixmonthstorecover,whichmightbe capturedinlongitudinalfollow-upandnotincross-sectionalstudies. For example, the COSCA-recommendations2 _{supporta recovery}

periodofoneyear.Unfortunately, welackdataonco-morbidities. However,aftercontrollingforage,sexandinitialrhythm,theeffectsize intermsofR2andpseudoR2wassmall.Althoughourresultsshow consistent findings across thedifferent measures ofHRQoL, the clinicalrelevanceofthesedifferencesisthereforestillunclear.

Itisnoteworthythatwe identifiedHRQoLdifferences between OHCAandIHCAsurvivorsinallmeasures exceptfor depression measuredwithHADSandanxiety/depressionmeasuredwith EQ-5D-5L. This finding was present in both adjusted and unadjusted analyses.Thus,itseemsthatproblemswithdepressionisnotrelated tothelocationfortheCA.Thesefindingshavenotbeenreported before. One explanation may be that many survivors reported problemswithdepressionbuttoalowextend.Thelowaveragescore for both depression measured by HADS and anxiety/depression measuredbyEQ-5D-5Lsupportthisexplanation.Itisalsoimportant torememberthatEQ-5D-5Lcombineanxietyanddepressioninthe samemeasurewhileHADShavespecificsubscalesforanxietyand depression.

Theaimofthisstudywasnottoinvestigatetheimportanceofage, sexandinitialrhythmforthesurvivorsHRQoL.However,theadjusted regressionmodelsshowedthatthesecovariatesplayedanimportant

Fig.2–MeandifferencesinEQ-5D-5L6monthsaftersurvivinganout-of-hospitalcardiacarrest(OHCA)comparedtoan

Table2_–Associationsbetweentypeofcardiacarrestandhealth-relatedqualityoflife(EQ-5D-5L)among2141

Swedishpatientssurviving6monthsafteracardiacarrestduring2014 2017,basedongeneralizedlogistic

regressionforordinaldependentvariables(theunconstrainedproportionaloddsmodel).

Outcomevariables Explanatoryvariables B(se) 95%CIforB p-value

Mobility OHCA 0.61(0.10) ( 0.80to 0.41) <0.001 Age 0.03(0.00) (0.03to0.04) <0.001 Femalesex 0.38(0.09) (0.20to0.56) <0.001 Non-shockablerhythma _{0.54(0.10) (0.33to0.74) <0.001}

Unknownrhythma _{0.40(0.12) (0.17to0.63) 0.001}

Modelstatistics: LRx2_{(5)=256.3,p<0.001,McFaddenR}2_=0.05

Self-care OHCA 0.53(0.13) ( 0.78to 0.27) <0.001 Age 0.02(0.00) (0.01to0.03) <0.001 Femalesex 0.21(0.12) ( 0.01to0.43) 0.068 Non-shockablerhythma _{0.66(0.13) (0.41to0.91) <0.001}

Unknownrhythma _{0.41(0.15) (0.12to0.71) 0.006}

Modelstatistics: LRx2_{(5)=110.4,p<0.001,McFaddenR}2_=0.04

Usualactivities OHCA 0.34(0.09) ( 0.51to 0.16) <0.001 Age 0.01(0.00) (0.01to 0.02) <0.001 Femalesex 0.30(0.09) (0.12to0.48) 0.001 Non-shockablerhythma _{0.32(0.10) (0.12to0.51) 0.002}

Unknownrhythma _{0.31(0.11) (0.08to0.53)}

Modelstatistics: LRx2(5)=83.4,p<0.001,McFaddenR2=0.02

Pain/discomfort OHCA 0.25(0.09) ( 0.42to 0.08) 0.004 Age 0.00(0.00) ( 0.01to0.01) 0.206 Femalesex 0.57(0.09) (0.39to0.74) <0.001 Non.shockablerhythma _{0.26(0.10) (0.07to0.46) 0.009}

Unknownrhythma _{0.29(0.11) (0.07to0.51) 0.009}

Modelstatistics: LRx2_{(5)=84.4,p<0.001,McFaddenR}2_=0.02

Anxiety/depression OHCA 0.09(0.09) ( 0.27to0.09) 0.340 Age 0.02(0.00) ( 0.03to 0.01) <0.001 Femalesex 0.54(0.09) (0.37to0.72) <0.001 Non-shockablerhythma _{0.23(0.10) (0.02to0.43) 0.029}

Unknownrhythma _{0.24(0.12) (0.02to0.47) 0.035}

Modelstatistics: LRx2_{(5)=83.6,p<0.001,McFaddenR}2_=0.02

B=regressioncoefficients;se=standarderror;CI=confidenceinterval.

a

Shockablerhythm=reference.

Table3_–Associationbasedonmultiplelinearregressionbetweentypeofcardiacarrestandhealth-relatedquality

oflife(EQVASandHospitalAnxietyandDepressionScale(HADS))among2141Swedishpatientssurviving6

monthsafterancardiacarrestduring2014 2017.

Outcomevariables Explanatoryvariables B(se) 95%CIforB p-value

EQVAS OHCA 5.67(0.98) (3.76to7.60) <0.001 Age 0.09(0.03) ( 0.16to 0.02) 0.008 Femalesex 3.80(0.99) ( 5.74to 1.86) <0.001 Non-shockablerhythma 3.70(1.13) ( 5.91to 1.49) 0.001 Unknownrhythma 3.11(1.25) ( 5.57to 0.66) 0.013 Modelstatistics: F(5,2134)=20.85,p<0.001,R2_=0.05

HADSanxiety OHCA 0.50(0.18) ( 0.86to 0.14) 0.006 Age 0.05(0.01) ( 0.06to 0.04) <0.001 Femalesex 1.00(0.18) (0.64to1.36) <0.001 Non-shockablerhythma _{0.50(0.21) (0.09to0.91) 0.016}

Unknownrhythma _{0.54(0.23) (0.09to1.00) 0.019}

Modelstatistics: F(5,2134)=20.68,p<0.001,R2_=0.05

HADSdepression OHCA 0.26(0.18) ( 0.62to0.09) 0.145 Age 0.00(0.01) ( 0.01to0.01) 0.931 Femalesex 0.63(0.18) (0.27to0.99) 0.001 Non-shockablerhythma _{0.43(0.21) (0.02to0.84) 0.039}

Unknownrhythma _{0.77(0.23) (0.31to1.22) 0.001}

Modelstatistics: F(5,2134)=6.80,p<0.001,R2_=0.02

B=unstandardizedregressioncoefficient;se=standarderror;CI=confidenceinterval.

roletoexplainthevarianceinHRQoL.Overall,higherage,femalesex and non-shockable rhythmwere associated with poorerHRQoL. RecentstudieshavealsoconcludedthatwomenreportworseHRQoL afterOHCA18 andIHCA4 comparedtomen.Interestingly,women moreoftensurviveanIHCAdespitedisadvantageousprerequisites such as higher age and more often non-shockable first rhythm comparedtomen.19

This study has some limitations that should be considered. According to the national Swedish Register of Cardiopulmonary Resuscitation,allsurvivorsshallundergoathirdregistrationincluding assessmentofHRQoL.Despitethis,theresponserateofallreported survivorsintheregistryduring2014 2017was55%and57%for OHCAandIHCAsurvivorsrespectivelyandthetwomajorreasonsto notparticipatewere“unknown”or“other”.Importantly,sincecognitive functionwasgivenasthereasontonotparticipatein7%and8%for OHCAandIHCArespectively,itislikelythattheHRQoLwouldbe

pooreramongnon-participants.Despitethismissingdata,thecurrent studyissofartheworld'slargestpublishedanditincludesthemajority ofcardiacarrestsurvivorsinanationwidepopulation-basedcohort. RegardingtheHRQoLassessmentsthatwereused,bothEQ-5D-5L andHADSaregenericinstruments,i.e.notspecificforcardiacarrest survivors.Itisthereforedifficulttodrawanystrongconclusionsabout theimpact thecardiacarresthavehad on thesurvivorsHRQoL. Likewise,wedonotknowifthereportedHRQoLisaresultofthe cardiacarrestorwasthesameasbeforethecardiacarrest.Until today, there exists no disease specific instruments to measure HRQoLincardiacarrestsurvivorsandthisisthereforealimitationfor allHRQoLresearchinthisfield.Finally,welackinformationregarding comparablecomorbiditiesandthedurationandetiologyofthecardiac arrestwhichmightbeofrelevanceforHRQoL.Strengthsincludethe nationalpopulation-basedall-encompassingcoverageandthelarge samplesize.

Fig.3–DistributionsofsymptomsofanxietyanddepressionusingtheHospitalAnxietyandDepressionScaleamong

Clinical implications for others might be related to our good experience fromaHRQoLassessmentin thenationalregistryas inspirationanddevelopment ofnationalguidelinesforfollow-up.20

IntegrationofHRQoLassessmentintoclinicalpraxisinfollow-upcare mightcontributetoidentifysurvivorswithpoorHRQoLandinneedof health-supportiveinterventions.

Inconclusion,HRQoLin cardiacarrestsurvivorsisin general good,butsurvivorsofIHCAreportmorehealthproblemscomparedto OHCAsurvivorsevenafteradjustmentforage,sexandinitialrhythm. Thereby, the current study supports that survivors of IHCA and survivorsofOHCAdifferandthatresearchdatagatheredfromoneof thesepopulationsmaynotbegeneralizabletotheother.

Conflict

of

interest

Nonedeclared.

Funding

T.D. was supported by the Stockholm County Council (clinical researchappointment).

Acknowledgement

TDwassupportedbyStockholmCounty(clinicalresearcher).

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