Long-term survival in patients with acute myocardial infarction and out-of-hospital cardiac arrest: A prospective cohort study

ContentslistsavailableatScienceDirect

Resuscitation

j o ur na l h o me pa g e:ww w . e l s e v i e r . c o m / l o c a t e / r e s u s c i t a t i o n

Clinical paper

Long-term survival in patients with acute myocardial infarction and out-of-hospital cardiac arrest: A prospective cohort study

Kristin M. Kvakkestad

, Leiv Sandvik

, Geir Øystein Andersen

, Kjetil Sunde

, Sigrun Halvorsen

aDepartmentofCardiology,OsloUniversityHospitalUlleval,Postboks4950Nydalen,0424Oslo,Norway

bInstituteofClinicalMedicine,UniversityofOslo,P.O.Box1072Blindern,0316Oslo,Norway

cOsloCentreforBiostatisticsandEpidemiology,ResearchSupportServices,P.O.Box1122Blindern,0317Oslo,Norway

dDepartmentofAnaesthesiology,DivisionofEmergenciesandCriticalCare,OsloUniversityHospitalUlleval,Postboks4950Nydalen,0424Oslo,Norway

a r t i c l e i n f o

Articlehistory:

Received18July2017

Receivedinrevisedform4November2017 Accepted15November2017

Keywords:

Out-of-hospitalcardiacarrest Acutemyocardialinfarction Long-termsurvival

a b s t r a c t

Aim:Tocompareshort-andlong-termsurvivalinpatientsadmittedtohospitalafteracutemyocardial infarction(AMI)withandwithoutout-of-hospitalcardiacarrest(OHCA).

Methods:ProspectivecohortstudyofallAMIpatientsadmittedtoOsloUniversityHospitalUllevalfrom September1,2005toDecember31,2011.All-causemortalitywasobtainedfromtheNorwegianCause ofDeathRegistrywithcensoringdateDecember31,2013.Cumulativesurvivalwasassessedwiththe Kaplan-MeierandtheLife-tablemethod.Logistic-andCoxregressionwereusedforriskcomparisons.

Results:Weidentified404 AMIpatients withOHCA and9425AMI patientswithout.AMI patients withoutOHCAwerecategorizedasST-elevationmyocardialinfarction(STEMI,n=4522)ornon-STEMI (NSTEMI,n=4903).Meanagewas63.6±standarddeviation(SD)12.5,63.8±13.1and69.7±13.6years inOHCA,STEMIandNSTEMI,respectively.Coronaryangiographywithsubsequentpercutaneouscoro- naryinterventionifindicated,wasperformedin87%ofOHCA,97%ofSTEMIand80%ofNSTEMIpatients.

Thirty-daysurvivalwas63%,94%and94%,and8-yearsurvivalwas49%,74%,and57%,respectively.Among patientssurvivingthefirst30days,nosignificantdifferenceinriskduringlong-termfollow-upwasfound (adjustedHazardRatio(aHR)OHCAvsSTEMI1.15[95%CI0.82–1.60],aHROHCAvsNSTEMI0.89[95%CI0.64-1.24]).

Conclusions:Long-termsurvivalafterOHCAduetoAMIwasgood,with49%ofadmittedpatientsbeing aliveaftereightyears.Althoughshort-termmortalityremainedhigh,OHCApatientsaliveafter30days hadsimilarlong-termriskasAMIpatientswithoutOHCA.

©2017TheAuthor(s).PublishedbyElsevierIrelandLtd.ThisisanopenaccessarticleundertheCC BY-NC-NDlicense(http://creativecommons.org/licenses/by-nc-nd/4.0/).

Introduction

Short-termprognosisofpatientswithout-of-hospitalcardiac arrest(OHCA)hasimprovedduringthelast15yearsduetoexten- siveeffortstooptimisebothpre-andin-hospitaltreatment[1–3].

Still,themajorityofpatientsdieafterOHCA,eitherpre-hospitaldue tolackofreturnofspontaneouscirculation(ROSC)orin-hospital afterROSCduetocerebralorothercomplications.

Standardisingpost-resuscitationcareimproved1-yearsurvival withgoodneurologicaloutcomeamongOHCApatientsadmitted toourhospitalin2003–2005[4],andiscurrentlyrecommendedin internationalguidelines[5].Thispost-resuscitationcarestrategy

∗ Correspondingauthorat:DepartmentofCardiology,OsloUniversityHospital Ulleval,Postboks4950Nydalen,0424Oslo,Norway.

E-mailaddress:[email protected](K.M.Kvakkestad).

includestargetedtemperaturemanagement(TTM),earlycoronary angiographywithsubsequentpercutaneouscoronaryintervention (PCI)ifindicated,aswellaslung-protectivemechanicalventila- tion,controlofbloodglucose,haemodynamicsandseizures,anda targetedprognosticationplan[5].

Ischaemicheartdiseaseandacutemyocardialinfarction(AMI) representthemostcommoncausesofOHCA[6,7].Somestudies havesuggestedthatshort-termprognosisafterOHCAduetoAMI mightbebetterthanforothercausesofOHCA[6,8–10].Ontheother hand,wehavepreviouslyshownthatAMIamongOHCApatients wasassociatedwithhighermortality[11].Withrespecttolong- termoutcomes,5-yearsurvivalof44%[7]and10-yearsurvivalof 12–38%[12]havebeenreportedinpatientswithOHCAofpresumed cardiaccause,dependingonselectioncriteria.Toourknowledge, long-termsurvival afterOHCA duetoAMIwithor withoutST- segmentelevationhasbeenspecificallyreportedinonlyonestudy

https://doi.org/10.1016/j.resuscitation.2017.11.047

0300-9572/©2017TheAuthor(s).PublishedbyElsevierIrelandLtd.ThisisanopenaccessarticleundertheCCBY-NC-NDlicense(http://creativecommons.org/licenses/by- nc-nd/4.0/).

Studypopulation

OsloUniversityHospital(OUH)Ullevalistheprimarymedical centreforapopulationof190,000inhabitants,andservesasasec- ondarycardiaccentreperformingcoronaryangiographyandPCI forapopulationofabout1400000millionpeopleinSouth-Eastern Norway.Thehospitalhasa24/7accesstocoronaryangiographyfor primaryPCI.Approximately4400coronaryangiogramsand1600 PCIsareperformedeveryyear.

All AMI patients admitted to OUH Ulleval from September 1, 2005, to December 31, 2011, were prospectively registered intoalocalAMIregistryuponadmission.Registrationclosedon December31,2011duetoestablishmentofanationalmyocardial infarctionregistrywithanewlegislationforuseofdata.Thereg- istrationprocedureandvariableshavebeendescribedpreviously [13].TheAMIdiagnosiswasbasedoncurrentinternationalcriteria [14,15]andtroponinTwasusedasthecardiacbiomarker.Patients withOHCAwereincludedintheAMIregistryiftheywereadmitted tothehospitalaliveorwithongoingcardiopulmonaryresuscitation (CPR)andanAMIdiagnosiswasconfirmed.

Onlythepatient´ısfirstAMIadmissionduringthestudyperiod wasincluded(Fig.1).AMIwithoutOHCAwereclassifiedasST- segment elevationmyocardial infarction (STEMI) or non-STEMI (NSTEMI)accordingtothediagnosticelectrocardiogram(ECG).As post-ROSCECGsmayhavenon-specificchanges[16],AMIpatients withOHCAwerenotfurtherclassifiedasSTEMIorNSTEMI,but analyzedasonesinglegroup(OHCA).

AllOHCApatientsin thepost-resuscitationcareperiodwere treated according to ourlocal standardised treatment protocol described elsewhere [4,11]. This treatmentprotocol [4,11] was introducedatOUHUllevalalreadyin2003,withonlyslightchanges overtheyears.RoutinecoronaryangiographywithPCIifindicated wasperformedimmediatelyafteradmissioninpatientswithST- segmentelevationontheECGandinotherpatientswithpresumed cardiaccauseatthecliniciansdiscretion.Comatosepatientswere treatedwithTTMat33^◦Cfor24hbeforegradualrewarmingtonor- mothermia.Themajorityofpatientsweretreatedincardiacand medicalintensivecareunits(ICUs).

Dataqualityandvalidation

Predefinedvariableswereregisteredintoacasereportformby theresponsiblephysicianduringadmission.Trainedstudyperson- nelcheckedthereportformforcompletenessanderrors,before enteringthe dataintoan electronicdatabasedeveloped bythe Mid-NorwayRegionalHealthAuthority.Acrosscheckagainstthe hospitaldischargeregisterwasperformedmonthlyand missing patientswereincludediftheymetthediagnosticcriteriaforAMI [14].Supplementarydata fortheOHCApatientswerecollected retrospectivelyfrom thehospital recordsaccording tothecore elementssuggested bytheUtsteinResuscitationRegistryOHCA Templates,whereavailable[17].

Cardiogenicshock was defined as a systolic blood pressure (SBP) <90mmHg withclinicalsigns of organ hypoperfusion, or needforinotropicdrugstokeepSBP>90mmHgintheabsenceof

(11%missing),timefromcardiacarresttobystanderCPR(24%miss- ing),timetoadvancedlifesupport(27%missing)andtimetoROSC (30%missing).

Follow-upandsurvival

Anydeathsanddeathdateswereobtainedbylinkageofthelocal AMIregistrywiththeNorwegianCauseofDeathRegistry,contain- ingvitalstatusthroughout2013.Patientswerecensoredifthey werealiveonDecember31,2013.Emigratedpatientswerecen- soredatdateoflasthospitalcontact(n=82).Follow-uptimewas calculatedfromadmissionuntilcensoringordeathbeforeJanuary 1,2014,whichevercamefirst,andvariedbetweenpatientsbecause ofthedynamiccohort.

Ethics

TheestablishmentofalocalAMIregistrywasapprovedbythe PrivacyProtectionOfficeratOUH.TheNorwegianDataProtection AuthorityprovidedconcessionfordatalinkagewiththeNorwegian CauseofDeathRegistry(January5,2012),withanexemptionfrom therequirementof patientconsent(TheMinistryofHealthand CareServices;November16,2011).Alldataforthis studywere anonymizedbeforeanalysis.

Statisticalanalyses

Categoricalvariables werepresented as percentagesof non- missingvalues;denominatorsmayvary.Continuousvariableswere presentedasmean±standarddeviation(SD)orasmedian(25,75th percentile)invariableswithmanyoutliers.Between-groupdiffer- encesforcategoricalvariableswereassessedwithChi-square-test, andforcontinuousvariableswiththetwo-samplet-testorMann- WhitneyUtest,asappropriate.

CumulativesurvivalwasillustratedwiththeKaplan-Meierplot anddifferences betweenOHCAversus STEMIandNSTEMIwere assessedwiththeLog-ranktest.TheLife-tablemethodwasusedto estimatethecumulativesurvivalat30daysandateightyears.Ina landmarkanalysis,weestimatedthelong-termsurvivalofpatients stillatriskatday30,toallowforadynamicpredictiondepend- ingonsurvivalinthefirst30days[18].Theproportionalhazards assumption,evaluatedusingthelog–logKaplan-Meierplot,was unmetusingCoxproportionalhazardsregressionforriskof30day- mortality.We thereforeusedlogisticregressiontocalculatethe oddsratio(OR)for30-daymortalityinOHCAversusSTEMIand NSTEMIpatients,adjustingforage(Model1)andforcharacteristics knownatadmission(age,gender,previoushypertension,diabetes mellitus,previousAMI,previousstroke,serum(s)-creatinineand pre-hospitalthrombolysis[STEMIonly])(Model2).Variableswith

>10%missingvalues(e.g.smokinghabits)werenotincludedinthe regressionanalyses.

WeusedtheCoxproportionalhazardsregressiontocalculate the hazard ratio (HR) for long-term mortality in OHCA versus STEMIandNSTEMI patientswhosurvived thefirst30days.The Coxmodelwasadjustedforage(Model1),andforage,gender, previoushypertension,diabetesmellitus,previousAMI,previous stroke,s-creatinineatadmission,pre-hospitalthrombolysis[STEMI

Fig.1. Cohortcreationflowchart.

AMI:Acutemyocardialinfarction.OHCA:Out-of-hospitalcardiacarrest;STEMI:ST-elevationmyocardialinfarction;NSTEMI:Non-STEMI.

Table1

Baselinecharacteristics,reperfusiontherapyandinvasivecoronaryprocedures.

AMIwithoutOHCA

AMI+OHCA,N=404 STEMI,N=4522 NSTEMI,N=4903 p-value¹ p-value²

Age,mean(SD) 63.6(12.5) 63.8(13.1) 69.7(13.6) 0.80 <0.001

Femalesex,n(%) 81(20.0) 1123(24.8) 1717(35.0) 0.03 <0.001

Previoushypertension,n(%) 142(35.1) 1553(34.3) 2113(43.1) 0.74 0.002

Diabetesmellitus,n(%) 49(12.3) 578(12.8) 930(19.0) 0.71 <0.001

Previousmyocardialinfarction,n (%)

68(17.0) 535(11.8) 1204(24.6) 0.003 <0.001

Previouscerebrovascularstroke,n (%)

16(4.0) 261(5.8) 550(11.2) 0.13 <0.001

Smoker-orex-smoker,n(%) 170(65.1) 2804(68.1) 2557(61.2) 0.33 0.20

S-creatinine(␮mol/l)atadmission, median(25,75thpercentile)

89(72,110) 74(63,88) 81(68,98) <0.001 <0.001

Reperfusiontherapyandinvasivecoronaryprocedures

Thrombolysis^a,n(%) 43(10.7) 488(10.8) 2(0) 0.93 –

Coronaryangiography,n(%) 353(87.4) 4366(96.6) 3910(79.7) <0.001 <0.001

PCI,n(%) 273(67.6) 3815(84.4) 2011(41.0) <0.001 <0.001

PrimaryPCI,n(%) 261(64.8) 3566(78.9) – <0.001 –

Door-to-balloon,minutes,median (25,75thpercentile)

40(31,70) 36(29,52) – <0.001 –

Symptom-to-balloon,minutes, median(25,75thpercentile)

183(125,291) 259(160,485) – <0.001 –

CABG,n(%) 14(3.5) 214(4.7) 513(10.5) 0.25 <0.001

Coronaryarterydiseaseinpatients undergoingcoronaryangiography, n(%)

N=353 N=4366 N=3910

Normalvesselsoratheromathosis 21(5.9) 127(2.9) 509(13.0) 0.002 <0.001

One-vesseldisease 146(41.4) 2022(46.3) 1460(37.3) 0.07 0.14

Multi-vesselorleftmaindisease 186(52.7) 2208(50.6) 1914(49.0) 0.44 0.18

OHCA:Out-of-hospitalcardiacarrest;STEMI:ST-elevationmyocardialinfarction;NSTEMI:Non-STEMI;PCI:Percutaneouscoronaryintervention;CABG:Coronaryartery byassgrafting;SD:standarddeviation.

p¹:OHCAvsSTEMI,p²:OHCAvsNSTEMI.

aThrombolysisprehospitaloratlocalhospital.

only],maximumtroponinT,coronaryangiography,PCI,cardiogenic shock,intraaorticballoonpump(IABP),heartfailure(withoutcar- diogenicshock)andatrialfibrillation/flutter(Model2).

AnalyseswereperformedwithSTATA13(StatacorpLP,Texas, USA). The study confines with the STROBE(STrengthening the ReportingofOBservationalstudiesinEpidemiology)checklistfor reportingofobservationalstudies[19].

Results Studypopulation

Atotalof9829AMIpatientswereincludedinthestudy(Fig.1):

404AMIpatientswithOHCAand9425without(4522STEMIand 4903NSTEMI).The baselinecharacteristics ofthethree patient groupsareshowninTable1and2.OHCApatientswere63.6±12.5 yearsofageandtheyweremorelikelytobemale(n=323;80.0%) comparedtoSTEMI(75.2%)andNSTEMI(65.0%)patients.Theircar- diovascularriskfactorprofilewassimilartothatofSTEMIpatients, exceptforahigherfrequencyofpreviousmyocardialinfarctionand

higherlevelsofs-creatinineuponadmission(Table1).Bystander CPRwasinitiatedin72.0%oftheOHCApatients,andVFwasthe firstmonitoredrhythmin82.0%(Table2).

In-hospitalmanagementandmortality

AmajorityofOHCApatientsunderwentcoronaryangiography (n=353;87.4%)andPCI(n=273;67.6%),althoughfewerthaninthe STEMIcohort(Table1).IntheOHCAgroup,door-to-balloontimes weresignificantlylonger,butsymptom-to-balloontimesshorter compared toSTEMI patients(Table 1).The frequencyof multi- vesselorleftmainstemdiseasewassimilarinallthreegroups (Table1).OHCApatientshadahigherburdenofin-hospitalcom- plicationscomparedtoAMIpatientswithoutOHCA,andassisted mechanicalventilationandIABPweremorefrequentlyused(Sup- plementary TableS1). Maximum troponin Tlevels (␮g/L) were median 3.14(1.32, 7.59) in OHCApatients, 3.79 (1.47,7.63) in STEMIpatients(p=0.04)and0.42(0.13,1.23)inNSTEMIpatients (p<0.001).

Defibrillation+CPR,n(%) 335(83.0)

Defibrillationonly,n(%) 53(12.8)

CPRonly,n(%) 15(3.7)

AchievedROSC,n(%) 381(94.5)

TimefromcardiacarresttoCPR,minutes* 0(0,2) TimefromcardiacarresttoROSC,minutes* 17(6,31)

TimefromALStoROSC,minutes* 10(4,25)

Comatoseathospitaladmission,n(%) 264(66.0)

Therapeutichypothermia,n(%) 206(53.0)

Systolicbloodpressureatadmission,mmHg* 115(95,132) Diastolicbloodpressureatadmission,mmHg* 70.5(60,82) Heartrateatadmission,beatsperminute* 80(70,98) ALS:Advancedlifesupport;AMI:Acutemyocardialinfarction;CPR:Cardiopul- monaryresuscitation;ECG: Electrocardiogram; OHCA: Out-of-hospitalcardiac arrest;ROSC:Returnofspontaneouscirculation;VF:Ventricularfibrillation.

*median(25,75thpercentile).

aAmbulancepersonnelorphysicianpresentatcardiacarrest.

Hospitalsurvival was275/404(68.1%) in thetotal cohort of OHCApatientsadmittedtoourhospital.Noneofthepatientsadmit- tedwithongoingCPR(n=22)achievedROSC.Hospitalsurvivalin OHCApatientsachievingROSCwas72.0%(275/382).AmongAMI patientswithoutOHCA,hospitalsurvivalwas95.7%(STEMI)and 95.8%(NSTEMI)(Table3).

30-daysurvival

30-daysurvivalwas63.4%,94.1%and93.8% amongadmitted OHCA,STEMIandNSTEMIpatients,respectively.Amarkeddiffer- enceinsurvivalwasseenthefirstdaysafteradmission,illustrated bytheKaplan-Meiersurvivalcurveforthefirst30days(Fig.2a).The crudeandadjustedORof30-daymortalityinOHCAversusSTEMI andNSTEMIareshowninTable4.InOHCApatientsachievingROSC, 30-daysurvivalwas67.0%(95%CI:62.1–71.5).

Long-termsurvival

Patientswerefollowedforuptoeightyears(medianfollow- uptime1446days[892,2125]).AmongOHCApatients,atotalof 195/404patientsdied.Cumulativesurvivalfromadmissiontoend offollow-upwas48.7%(95%CI:43.7-54.1)inOHCApatients,and 77.6% (95% CI: 70.6–83.1) in OHCA patients surviving the first 30days(Table3).

Fig.2billustratesthatOHCApatientssurvivingthefirst30days hadestimatedsimilar8-yearsurvivalcomparedtoSTEMIpatients.

Thecrude HRrevealedahigherriskofdeathforOHCAthanfor

paredwithSTEMIandNSTEMIpatientswithoutOHCA.

Discussion

Inthislargestudyof9829AMIpatients,wefoundalower30-day survivalinOHCApatientscomparedtoSTEMIandNSTEMIpatients.

However,afteramaximumfollow-uptimeofeightyears,almost halfoftheadmittedOHCApatientswerestillalive.Interestingly,in thosepatientssurvivingthefirst30days,nosignificantdifference inlong-termriskwasfoundbetweenAMIpatientswithandwith- outOHCA,afteradjustmentforageandotherconfounders.Among OHCApatientssurvivingthefirst30days,the8-yearsurvivalrate wasashighas77.6%.

Thehighershort-termmortalityinOHCApatientswasmainly duetoearlydeathsoccurringthefirst4–5daysafteradmission,and thisisinaccordancewithpreviousstudiesonSTEMIpatientswith andwithoutOHCA[6,10,20,21].However,a30-daysurvivalrateof 63.4%inunselectedAMIpatientswithOHCAishigherthaninmost previousreportsofshort-termsurvivalinOHCAwithoutobvious non-cardiacorigin[6,7,12,22,23].OurOHCApatientgroupwashet- erogeneous,withahighproportionofpatientsbeingawakeupon hospitaladmission.Ontheotherhand,22patientshadongoingCPR neverachievingROSC,anddiedshortlyafteradmission.Allpatients wereaggressivelytreatedwithhighratesofcoronaryangiography andPCI,previouslyshowntobeassociatedwithimprovedoutcome [7,23],aswellasgoodqualitypost-ROSCcare[16,24–26].

The8-yearsurvivalrateofnearly80%inOHCApatientswhosur- viveduntil30daysafteradmissionissimilartoresultsfromSideris etal.reportinga5-yearsurvival ratefromdischargeof82%[8].

Otherreportsoflong-termsurvivalinOHCApatientsofpresumed cardiacoriginisvarying,with5-yearsurvivalafterdischargeof 41%[27],64%[28]and84%[7],and10-yearsurvivalafterdisharge of46%[29].Anotherstudyreported10-yearsurvivalfromadmis- sionof12–38%dependingonwhethercoronaryangiographyand PCIwereperformedornot[12].Acomparisonofsurvivalbetween studiesisnotstraightforwardduetodifferentaetiologies,inclu- sioncriteriaandtreatmentstrategiesforOHCApatients.However, thegoodlong-termprognosisofOHCApatientswhosurviveduntil 30daysinourstudyispromising.Ourfollow-uptimewaslonger thaninmostotherstudies,increasingtheaccuracyoftheresults.

Previousstudieshave reportedasimilarprognosisafterdis- chargeforSTEMIpatientswithandwithoutOHCA;butinmost ofthesestudiespatientswerehighlyselected[10,20,21].Toour knowledge,wearethefirsttocomparesurvivalinunselectedAMI

Table3

CumulativesurvivalinAMIpatientswithandwithoutOHCA(Lifetablemethod).

NoOHCA

OHCA,N=404 STEMI,N=4522 NSTEMI,N=4903

Hospitalsurvival,n(%) 275(68.1) 4328(95.7) 4698(95.8)

30-daysurvival,% 63.4(58.5–67.9) 94.1(93.3–94.7) 93.8(93.0–94.4)

8-yearsurvival(admissiontoendofstudy*),% 48.7(43.1–54.1) 73.5(71.2–75.6) 57.3(55.0–59.4)

8-yearsurvival(day30toendofstudy*),% 77.6(70.6–83.1) 77.7(75.2–80.0) 60.7(58.3–63.1)

Resultsaregivenaspercentagewith95%confidenceinterval.

*Medianfollow-uptime:1446days(25,75thpercentile:892,2125).

AMI:Acutemyocardialinfarction;OHCA:Out-of-hospitalcardiacarrest;STEMI:ST-segmentelevationmyocardialinfarction;NSTEMI:Non-STEMI;CI:Confidenceinterval.

Fig.2. Short-andlong-termsurvival.

2a.Kaplan-Meiercurvefor30-daysurvival.

2b.Kaplan-Meiercurvewithlandmarkanalysis:Long-termsurvivalamongpatientssurvivingthefirst30days.

AMI:Acutemyocardialinfarction;OHCA:out-of-hospitalcardiacarrest;STEMI:ST-elevationmyocardialinfarction(noOHCA);NSTEMI:Non-STEMI(noOHCA).Median follow-up:1446days(25,75thpercentile:892,2125).

Table4

Riskof30-daymortalityandlong-termmortalityafter30days.

OHCAvsSTEMI p-value OHCAvsNSTEMI p-value

30-daymortality:

CrudeOR(95%CI) 9.18(7.24–11.6) <0.001 8.60(6.81–10.9) <0.001

Model1:Age-adjustedOR(95%CI) 12.4(9.53–16.2) <0.001 19.4(14.6–25.8) <0.001

Model2:Multivariate^aadjustedOR(95%CI) 10.6(7.87–14.4) <0.001 18.2(13.1–25.1) <0.001

Landmarkanalysis:Mortalityfromday30toendofstudy*:

CrudeHR(95%CI) 1.45(1.08–1.95) 0.01 0.62(0.47–0.83) 0.001

Model1:Age-adjustedHR(95%CI) 1.78(1.32–2.40) <0.001 1.12(0.83–1.50) 0.46

Model2:Multivariate^badjustedHR(95%CI) 1.15(0.82–1.60) 0.42 0.89(0.64–1.24) 0.50

AMI:Acutemyocardialinfarction;OHCA:Out-of-hospitalcardiacarrest;STEMI:ST-elevationmyocardialinfarction;NSTEMI:Non-STEMI;OR:Oddsratio;HR:Hazardratio;

CI:Confidenceinterval.

*Medianfollow-up:1446days(25,75thpercentile:892,2125).

aAge,femalegender,previoushypertension,diabetesmellitus,previousstroke,previousmyocardialinfarction,s-creatinine(mmol/l)atadmission.

bAllfactorsin^a+MaxtroponinT(␮g/l),coronaryangiography,percutaneouscoronaryintervention,cardiogenicshock,heartfailure,atrialfibrillation/flutter,intraaortic balloonpump.

similarforOHCAandSTEMIpatients,exceptforahigherfrequency ofpreviousmyocardialinfarctionandhigherlevelsofs-creatinine uponadmission,probablycontributingtothehigherunadjusted riskinOHCAcomparedtoSTEMIpatients.Thelowerratesofcoro- naryangiographyinNSTEMIcomparedtoSTEMIpatientsreflect theguideline-recommendedmanagementduringthestudyperiod, taking into account risk stratification and comorbidities before selectinganinvasivestrategyinNSTEMIpatients[30].AlsoinOHCA patients,acutecoronaryangiographywasnotperformedroutinely inallpatients,duetolackofconsensusontheuseofthisproce- dureifabsentST-segmentelevationinthepost-ROSCECG[16].The between-groupdifferencesinuseofcoronaryangiographyandPCI wereadjustedforintheregressionanalysesestimatinglong-term riskinpatientsaliveafter30days.Ourresultsshouldencouragefur- theroptimalisationofpre-hospitaltreatmentandpost-ROSCcare ofAMIpatientswithOHCA,notonlyduetothepromisinglong-term resultsbutalsototrytoimproveshort-termprognosis.

Thestrengthsofthepresentstudyarea completelong-term follow-up of a high number of unselected AMI patients, with detaileddescriptionofriskfactorsandtreatment,aswellasesti- matesof long-term survival in AMIpatients withand without OHCA.There werefew missing values in theclinical variables, ensuringadetaileddescriptionofthestudypopulationandalower probabilityofoverestimatingrisk.Themainlimitationofthestudy wastheobservationalnaturesothateffectofinterventionsand treatmentcould not be determined. We did not register clini- calfactorssuchasheartrate,bloodpressureandmedicationat admission,norleftventricularejectionfraction,which couldbe possibleconfoundersinestimatingrisk.Furthermore,wedidnot haveinformationaboutpost-dischargetreatment,suchasmedi- cations,implantablecardioverterdefibrillatorsorqualityoflifein thesurvivingpatients.Variableswith>10%missingvalueswere notincludedintheregressionanalyses.Whethertheseorunmea- suredvariablescontributedtoconfoundingintheestimatedHRfor OHCApatientscomparedtoSTEMIandNSTEMIremainsunknown.

Reportedmedian timesfromcardiacarrest toinitiationof CPR, advancedlifesupportandtoachievementofROSC,aresomewhat uncertainduetomanymissingvalues.Finally,ourstudywascon- ductedinasinglecentrewitha24/7PCIserviceandanestablished post-resuscitationprotocol,andtheresultsarenotnecessarilygen- eralizabletoallAMIpatientswithOHCA.Althoughthemajorityof STEMIandresuscitatedOHCApatientsintheregionarenormally admittedtoourhospital, welack informationabout thoseAMI patientsnotbeingadmitted.Futurestudiescanrevealwhetherour resultsarereproducibleforpatientstreatedinothercardiaccen- treswith24/7coronaryangiography/PCIserviceandstandardised post-resuscitationcare.

Conclusion

Long-termsurvivalinAMIpatientswithOHCAwasgoodwith 49%ofpatientsbeingaliveaftereightyearsoffollow-up.Although short-termmortalityremainedhighinAMIpatientswithOHCA, patientssurvivingthefirst30dayshadsimilarchanceofsurvival duringeightyearsoffollow-upasAMIpatientswithoutOHCA.

andqualitycontrol.We thanktheMid-NorwayRegionalHealth AuthorityforsupplyoftheelectronicdatabaseandtheNorwegian CauseofDeathregistryformortalitydata.Thestudywasfunded bygrantnumber2013028fromtheScientificBoardoftheSouth- easternNorwayRegionalHealthAuthority,Hamar,Norway.The fundershadnoroleinstudydesign,analysisandinterpretationof thedata,writingorthedecisiontosubmitthisarticle.

AppendixA. Supplementarydata

Supplementarydataassociatedwiththisarticlecanbefound,in theonlineversion,athttps://doi.org/10.1016/j.resuscitation.2017.

11.047.

References

[1].Lund-KordahlI,OlasveengenTM,LoremT,SamdalM,WikL,SundeK.Improving outcomeafterout-of-hospitalcardiacarrestbystrengtheningweaklinksofthe localchainofsurvival;qualityofadvancedlifesupportandpost-resuscitation care.Resuscitation2010;81:422–6.

[2].WongMK,MorrisonLJ,QiuF,AustinPC,CheskesS,DorianP,etal.Trendsinshort- andlong-termsurvivalamongout-of-hospitalcardiacarrestpatientsaliveat hospitalarrival.Circulation2014;130:1883–90.

[3].WissenbergM,FolkeF,HansenCM,LippertFK,KragholmK,RisgaardB,etal.

Survivalafterout-of-Hospitalcardiacarrestinrelationtoageandearlyiden- tificationofpatientswithminimalchanceoflong-termsurvival.Circulation 2015;131:1536–45.

[4].SundeK,PytteM,JacobsenD,MangschauA,JensenLP,SmedsrudC,etal.Imple- mentationofastandardisedtreatmentprotocolforpostresuscitationcareafter out-of-hospitalcardiacarrest.Resuscitation2007;73:29–39.

[5].NolanJP,SoarJ,CariouA,CronbergT,MoulaertVR,DeakinCD,etal.European resuscitationcouncilandEuropeansocietyofintensivecaremedicineguidelines forpost-resuscitationcare2015:section5oftheeuropeanresuscitationcouncil guidelinesforresuscitation2015.Resuscitation2015;95:202–22.

[6].LarsenJM,RavkildeJ.Acutecoronaryangiographyinpatientsresuscitatedfrom out-of-hospitalcardiacarrest–asystematicreviewandmeta-analysis.Resusci- tation2012;83:1427–33.

[7].BergmanR,HiemstraB,NieuwlandW,LipsicE,AbsalomA,vanderNaaltJ, etal.Long-termoutcomeofpatientsafterout-of-hospitalcardiacarrestinrela- tiontotreatment:asingle-centrestudy.EurHeartJAcuteCardiovascCare 2016;5:328–38.

[8].SiderisG,VoicuS,YannopoulosD,DillingerJG,AdjedjJ,DeyeN,etal.Favourable 5-yearpostdischargesurvival ofcomatosepatientsresuscitatedfrom out- of-hospitalcardiacarrest,managedwithimmediatecoronaryangiogramon admission.EurHeartJAcuteCardiovascCare2014;3:183–91.

[9].FothergillRT,WatsonLR,VirdiGK,MooreFP,WhitbreadM.Survivalofresus- citatedcardiacarrestpatientswithST-elevationmyocardialinfarction(STEMI) conveyeddirectlytoaheartattackcentrebyambulanceclinicians.Resuscitation 2014;85:96–8.

[10].DemirelF,RasoulS,ElvanA,OttervangerJP,DambrinkJH,GosselinkAT,etal.

Impactofout-of-hospitalcardiacarrestduetoventricularfibrillationinpatients withST-elevationmyocardialinfarctionadmittedforprimarypercutaneous coronaryintervention:ImpactofventricularfibrillationinSTEMIpatients.Eur HeartJAcuteCardiovascCare2015;4:16–23.

[11].TomteO,AndersenGO,JacobsenD,DraegniT,AuestadB,SundeK.Strong weakaspectsofanestablishedpost-resuscitationtreatmentprotocol-afive-year observationalstudy.Resuscitation2011;82:1186–93.

[12].GeriG,DumasF,BougouinW,VarenneO,DaviaudF,PeneF,etal.Immedi- atepercutaneouscoronaryinterventionisassociatedwithimprovedshort-and long-termsurvivalafterout-of-hospitalcardiacarrest.CircCardiovascInterv 2015;8:e002303,http://dx.doi.org/10.1161/CIRCINTERVENTIONS.114.002303.

[13].KvakkestadKM,AbdelnoorM,ClaussenPA,EritslandJ,FossumE,Halvorsen S.Long-termsurvivalinoctogenariansandolderpatientswithST-elevation myocardialinfarctionintheeraofprimaryangioplasty:aprospectivecohort study.EurHeartJAcuteCardiovascCare2016;5:243–52.

[14].ThygesenK,AlpertJS,WhiteHD.Universaldefinitionofmyocardialinfarction.

EurHeartJ2007;28:2525–38.

[15].AlpertJS,ThygesenK,AntmanE,BassandJP.Myocardialinfarctionredefined–a consensusdocumentofTheJointEuropeanSocietyofCardiology/AmericanCol-

legeofCardiologyCommitteefortheredefinitionofmyocardialinfarction.JAm CollCardiol2000;36:959–69.

[16].Staer-JensenH,NakstadER,FossumE,MangschauA,EritslandJ,DraegniT,etal.

Post-resuscitationECGforselectionofpatientsforimmediatecoronaryangiog- raphyinout-of-hospitalcardiacarrest.CircCardiovascInterv2015:e002784, http://dx.doi.org/10.1161/CIRCINTERVENTIONS.115.002784.

[17].JacobsI,NadkarniV,BahrJ,BergRA,BilliJE,BossaertL,etal.Cardiacarrest andcardiopulmonaryresuscitationoutcomereports:updateandsimplification oftheUtsteintemplatesforresuscitationregistries.Astatementforhealthcare professionalsfromataskforceoftheinternationalliaisoncommitteeonresusci- tation(AmericanHeartAssociation,EuropeanResuscitationCouncil,Australian ResuscitationCouncil,NewZealandResuscitationCouncil,HeartandStroke FoundationofCanada,InterAmericanHeartFoundation,ResuscitationCouncil ofSouthernAfrica).Resuscitation2004;63:233–49.

[18].vanHouwelingenHC.Dynamicpredictionbylandmarkingineventhistoryanal- ysis.ScandJStat2006;34:70–85.

[19].STROBEstatement–checklistofitemsthatshouldbeincludedinreportsofobser- vationalstudies(STROBEinitiative).IntJPublicHealth2008;53:3–4.

[20].BendzB,EritslandJ,NakstadAR,BrekkeM,KlowNE,SteenPA,etal.Long- termprognosisafterout-of-hospitalcardiacarrestandprimarypercutaneous coronaryintervention.Resuscitation2004;63:49–53.

[21].LettieriC,SavonittoS,DeServiS,GuagliumiG,BelliG,RepettoA,etal.Emergency percutaneouscoronaryinterventioninpatientswithST-elevationmyocardial infarctioncomplicatedbyout-of-hospitalcardiacarrest:earlyandmedium- termoutcome.AmHeartJ2009;75:e1.

[22].HollenbeckRD,McPhersonJA,MooneyMR,UngerBT,PatelNC,McMullan JrPW,etal.Earlycardiaccatheterizationisassociatedwithimprovedsur- vivalincomatosesurvivorsofcardiacarrestwithoutSTEMI.Resuscitation 2014;85:88–95.

[23].DumasF,CariouA,Manzo-SilbermanS,GrimaldiD,VivienB,RosencherJ, etal.Immediatepercutaneouscoronaryinterventionisassociatedwithbet- tersurvival afterout-of-hospital cardiacarrest:insightsfromthePROCAT (ParisianRegionOutofhospitalCardiacArresT)registry.CircCardiovascInterv 2010;3:200–7.

[24].LanghelleA,TyvoldSS,LexowK,HapnesSA,SundeK,SteenPA.In-hospitalfac- torsassociatedwithimprovedoutcomeafterout-of-hospitalcardiacarrest:a comparisonbetweenfourregionsinNorway.Resuscitation2003;56:247–63.

[25].HerlitzJ,EngdahlJ,SvenssonL,AngquistKA,SilfverstolpeJ,HolmbergS.Major differencesin1-monthsurvivalbetweenhospitalsinSwedenamonginitial survivorsofout-of-hospitalcardiacarrest.Resuscitation2006;70:404–9.

[26].GaieskiDF,BandRA,AbellaBS,NeumarRW,FuchsBD,KolanskyDM,etal.

Early goal-directedhemodynamicoptimization combinedwith therapeutic hypothermiaincomatosesurvivorsofout-of-hospitalcardiacarrest.Resusci- tation2009;80:418–24.

[27].NaessAC,SteenPA.Longtermsurvivalandcostsperlifeyeargainedafterout- of-hospitalcardiacarrest.Resuscitation2004;60:57–64.

[28].DumasF,WhiteL,StubbsBA,CariouA,ReaTD.Long-termprognosisfollowing resuscitationfromoutofhospitalcardiacarrest:roleofpercutaneouscoronary interventionandtherapeutichypothermia.JAmCollCardiol2012;60:21–7.

[29].HollerNG,MantoniT,NielsenSL,LippertF,RasmussenLS.Long-termsurvival afterout-of-hospitalcardiacarrest.Resuscitation2007;75:23–8.

[30].WijnsW,KolhP,DanchinN,DiMarioC,FalkV,FolliguetT,etal.Guidelineson myocardialrevascularization.EurHeartJ2010;31:2501–55.