2024ESC急性肺栓塞诊断和管理指南(英文版)初中教育

1/12023ESC急性肺栓塞诊断和管理指南(英文版)-初中教育

ESCGUIDELINES2023ESCGuidelinesonthediagnosisand

managementofacutepulmonaryembolism

TheTaskForcefortheDiagnosisandManagementofAcute

PulmonaryEmbolismoftheEuropeanSocietyofCardiology(ESC)EndorsedbytheEuropeanRespiratorySociety(ERS)

Authors/TaskForceMembers:StavrosKonstantinides*(Chairperson)(Germany/Greece),AdamTorbicki*(Co-chairperson)(Poland),GiancarloAgnelli(Italy),NicolasDanchin(France),DavidFitzmaurice(UK),NazzarenoGalie`(Italy),

J.SimonR.Gibbs(UK),MennoHuisman(TheNetherlands),MarcHumbert?(France),NilsKucher(Switzerland),IreneLang(Austria),MareikeLankeit(Germany),JohnLekakis(Greece),ChristophMaack(Germany),EckhardMayer(Germany),

NicolasMeneveau(France),ArnaudPerrier(Switzerland),PiotrPruszczyk(Poland),LarsH.Rasmussen(Denmark),ThomasH.Schindler(USA),PavelSvitil(Czech

Republic),AntonVonkNoordegraaf(TheNetherlands),JoseLuisZamorano(Spain),MaurizioZompatori(Italy)

ESCCommitteeforPracticeGuidelines(CPG):JoseLuisZamorano(Chairperson)(Spain),StephanAchenbach(Germany),HelmutBaumgartner(Germany),JeroenJ.Bax(Netherlands),HectorBueno(Spain),VeronicaDean(France),ChristiDeaton(UK),?etinErol(Turkey),RobertFagard(Belgium),RobertoFerrari(Italy),DavidHasdai(Israel),ArnoHoes(Netherlands),PaulusKirchhof(Germany/UK),JuhaniKnuuti(Finland),PhilippeKolh(Belgium),PatrizioLancellotti(Belgium),AlesLinhart(CzechRepublic),PetrosNihoyannopoulos(UK),MassimoF.

Piepoli*Correspondingauthors.StavrosKonstantinides,CentreforThrombosisandHemostasis,JohannesGutenbergUniversityofMainz,UniversityMedicalCentreMainz,Langenbeckstrasse1,55131Mainz,Germany.Tel:+496131176255,Fax:+496131173456.Email:stavros.konstantinides@unimedizin-mainz.de,andDepartmentofCardiology,DemocritusUniversityofThrace,Greece.Email:skonst@med.duth.gr.

AdamTorbicki,DepartmentofPulmonaryCirculationandThromboembolicDiseases,MedicalCentreofPostgraduateEducation,ECZ-Otwock,Ul.Borowa14/18,05-400Otwock,Poland.Tel:+48227103052,Fax:+4822710315.Email:adam.torbicki@ecz-otwock.pl.

?RepresentingtheEuropeanRespiratorySociety

OtherESCentitieshavingparticipatedinthedevelopmentofthisdocument:

ESCAssociations:AcuteCardiovascularCareAssociation(ACCA),EuropeanAssociationforCardiovascularPreventionhowever,theESCGuidelinesdonotoverride,inanywaywhatsoever,theinpidualresponsibilityofhealthprofessionalstomakeappropriateandaccuratedecisionsinconsiderationofeachpatient’shealthconditionandinconsultationwiththatpatientand,whereappropriateand/ornecessary,thepatient’scaregiver.NordotheESCGuidelinesexempthealthprofessionalsfromtakingintofullandcarefulconsiderationtherelevantof?cialupdatedrecommendationsorguidelinesissuedbythecompetentpublichealthauthorities,inordertomanageeachpatient’scaseinlightofthescienti?callyaccepteddatapursuanttotheirrespectiveethicalandprofessionalobligations.Itisalsothehealthprofessional’sresponsibilitytoverifytheapplicablerulesandregulationsrelatingtodrugsandmedicaldevicesatthetimeofprescription.

NationalCardiacSocietiesdocumentreviewers:listedintheAppendix.

&TheEuropeanSocietyofCardiology2023.Allrightsreserved.Forpermissionspleaseemail:journals.permissions@e43f5da204a1b0717ed5dd2a.EuropeanHeartJournaldoi:10.1093/eurheartj/ehu283

EuropeanHeartJournalAdvanceAccesspublishedAugust29,2023atFujianUniversityofTraditionalChineseMedicineonAugust30,2023e43f5da204a1b0717ed5dd2a/Downloadedfrom

(Italy),PiotrPonikowski(Poland),PerAntonSirnes(Norway),JuanLuisTamargo(Spain),MichalTendera(Poland),AdamTorbicki(Poland),WilliamWijns(Belgium),StephanWindecker(Switzerland).

DocumentReviewers:?etinErol(CPGReviewCoordinator)(Turkey),DavidJimenez(ReviewCoordinator)(Spain),WalterAgeno(Italy),StefanAgewall(Norway),RiccardoAsteggiano(Italy),RupertBauersachs(Germany),

CeciliaBecattini(Italy),HenriBounameaux(Switzerland),HarryR.Bu¨ller(Netherlands),ConstantinosH.Davos(Greece),ChristiDeaton(UK),Geert-JanGeersing(Netherlands),MiguelAngelGo′mezSanchez(Spain),

JeroenHendriks(Netherlands),ArnoHoes(Netherlands),MustafaKilickap(Turkey),ViacheslavMareev(Russia),ManuelMonreal(Spain),JoaoMorais(Portugal),PetrosNihoyannopoulos(UK),BogdanA.Popescu(Romania),OlivierSanchez?(France),AlexC.Spyropoulos(USA).

ThedisclosureformsprovidedbytheexpertsinvolvedinthedevelopmentoftheseguidelinesareavailableontheESCwebsitee43f5da204a1b0717ed5dd2a/guidelines.

KeywordsGuidelines?Pulmonaryembolism?Venousthrombosis?Shock?Hypotension?Chestpain?Dyspnoea?Heartfailure?Diagnosis?Treatment–Anticoagulation?Thrombolysis

TableofContents

Abbreviationsandacronyms(3)

1.Preamble(3)

2.Introduction(4)

2.1Epidemiology(5)

2.2Predisposingfactors(5)

2.3Naturalhistory(6)

2.4Pathophysiology(6)

2.5Clinicalclassi?cationofpulmonaryembolismseverity(7)

3.Diagnosis(7)

3.1Clinicalpresentation(7)

3.2Assessmentofclinicalprobability(8)

3.3D-dimertesting(8)

3.4Computedtomographicpulmonaryangiography(10)

3.5Lungscintigraphy(11)

3.6Pulmonaryangiography(11)

3.7Magneticresonanceangiography(11)

3.8Echocardiography(11)

3.9Compressionvenousultrasonography(12)

3.10.Diagnosticstrategies(12)

3.10.1Suspectedpulmonaryembolismwithshock

orhypotension(12)

3.10.2Suspectedpulmonaryembolismwithout

shockorhypotension(13)

3.11.Areasofuncertainty(14)

4.Prognosticassessment(15)

4.1Clinicalparameters(15)

4.2Imagingoftherightventriclebyechocardiography

orcomputedtomographicangiography(16)

4.3Laboratorytestsandbiomarkers(17)

4.3.1Markersofrightventriculardysfunction(17)

4.3.2Markersofmyocardialinjury(17)

4.3.3Other(non-cardiac)laboratorybiomarkers(18)

4.4Combinedmodalitiesandscores(19)

4.5Prognosticassessmentstrategy(19)

5.Treatmentintheacutephase(20)

5.1Haemodynamicandrespiratorysupport(20)

5.2Anticoagulation(20)

5.2.1Parenteralanticoagulation(20)

5.2.2VitaminKantagonists(21)

5.2.3Neworalanticoagulants(22)

5.3Thrombolytictreatment(23)

5.4Surgicalembolectomy(24)

5.5Percutaneouscatheter-directedtreatment(24)

5.6Venous?lters(24)

5.7Earlydischargeandhometreatment(25)

5.8Therapeuticstrategies(26)

5.8.1Pulmonaryembolismwithshockorhypotension

(high-riskpulmonaryembolism)(26)

5.8.2Pulmonaryembolismwithoutshockorhypotension

(intermediate-orlow-riskpulmonaryembolism)(26)

5.9Areasofuncertainty(27)

6.Durationofanticoagulation(29)

6.1Neworalanticoagulantsforextendedtreatment(30)

7.Chronicthromboembolicpulmonaryhypertension(31)

7.1Epidemiology(31)

7.2Pathophysiology(31)

7.3Clinicalpresentationanddiagnosis(31)

7.4Treatmentandprognosis(32)

8.Speci?cproblems(34)

8.1Pregnancy(34)

8.1.1Diagnosisofpulmonaryembolisminpregnancy(34)

8.1.2Treatmentofpulmonaryembolisminpregnancy(34)

8.2Pulmonaryembolismandcancer(35)

8.2.1Diagnosisofpulmonaryembolisminpatientswith

cancer(35)

8.2.2Prognosisforpulmonaryembolisminpatientswith

cancer(35)

8.2.3Managementofpulmonaryembolisminpatientswith

cancer(35)

8.2.4Occultcancerpresentingasunprovokedpulmonary

embolism(36)

8.3Non-thromboticpulmonaryembolism(36)

8.3.1Septicembolism(36)

8.3.2Foreign-materialpulmonaryembolism(36)

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8.3.3Fatembolism(36)

8.3.4Airembolism(37)

8.3.5Amniotic?uidembolism(37)

8.3.6Tumourembolism(37)

9.Appendix(37)

References(37)

Abbreviationsandacronyms

ACSacutecoronarysyndrome

AMPLIFYApixabanfortheInitialManagementofPulmonaryEmbolismandDeep-VeinThrombosisasFirst-line

Therapy

aPTTactivatedpartialthromboplastintime

b.i.d.bisindiem(twicedaily)

b.p.m.beatsperminute

BNPbrainnatriureticpeptide

BPbloodpressure

CIcon?denceinterval

COcardiacoutput

COPDchronicobstructivepulmonarydisease

CPGCommitteeforPracticeGuidelines

CRNMclinicallyrelevantnon-major

CTcomputedtomographic/tomogram

CTEPHchronicthromboembolicpulmonaryhypertensionCUScompressionvenousultrasonography

DSAdigitalsubtractionangiography

DVTdeepveinthrombosis

ELISAenzyme-linkedimmunosorbentassay

ESCEuropeanSocietyofCardiology

H-FABPheart-typefattyacid-bindingprotein

HITheparin-inducedthrombocytopenia

HRhazardratio

ICOPERInternationalCooperativePulmonaryEmbolismRegistry

ICRPInternationalCommissiononRadiologicalProtectionINRinternationalnormalizedratio

iPAHidiopathicpulmonaryarterialhypertension

IVCinferiorvenacava

LMWHlowmolecularweightheparin

LVleftventricle/leftventricular

MDCTmulti-detectorcomputedtomographic(angiography)MRAmagneticresonanceangiography

NGALneutrophilgelatinase-associatedlipocalin

NOAC(s)Non-vitaminK-dependentneworalanticoagulant(s)NT-proBNPN-terminalpro-brainnatriureticpeptide

o.d.omnidie(everyday)

ORoddsratio

PAHpulmonaryarterialhypertension

PEpulmonaryembolism

PEApulmonaryendarterectomy

PEITHOPulmonaryEmbolIsmTHrOmbolysistrial

PESIpulmonaryembolismseverityindex

PHpulmonaryhypertensionPIOPEDProspectiveInvestigationOnPulmonaryEmbolismDiagnosis

PVRpulmonaryvascularresistance

RIETERegistroInformatizadodelaEnfermedadThrom-boembolicavenosa

RRrelativerisk

rtPArecombinanttissueplasminogenactivator

RVrightventricle/ventricular

SPECTsinglephotonemissioncomputedtomographysPESIsimpli?edpulmonaryembolismseverityindexTAPSEtricuspidannulusplanesystolicexcursion

Tctechnetium

TOEtransoesophagealechocardiography

TTRtimeintherapeuticrange

TVtricuspidvalve

UFHunfractionatedheparin

V/Qscanventilation–perfusionscintigraphy

VKAvitaminKantagonist(s)

VTEvenousthromboembolism

1.Preamble

Guidelinessummarizeandevaluateallavailableevidenceatthetimeofthewritingprocess,onaparticularissuewiththeaimofassistinghealthprofessionalsinselectingthebestmanagementstrategiesforaninpidualpatient,withagivencondition,takingintoaccounttheimpactonoutcome,aswellastherisk-bene?t-ratioofparticulardiag-nosticortherapeuticmeans.Guidelinesandrecommendationsshouldhelpthehealthprofessionalstomakedecisionsintheirdailypractice.However,the?naldecisionsconcerninganinpidualpatientmustbemadebytheresponsiblehealthprofessional(s)inconsultationwiththepatientandcaregiverasappropriate.

AgreatnumberofGuidelineshavebeenissuedinrecentyearsbytheEuropeanSocietyofCardiology(ESC)aswellasbyothersoci-etiesandorganisations.Becauseoftheimpactonclinicalpractice,qualitycriteriaforthedevelopmentofguidelineshavebeenestab-lishedinordertomakealldecisionstransparenttotheuser.TherecommendationsforformulatingandissuingESCGuidelinescanbefoundontheESCWebSite(e43f5da204a1b0717ed5dd2a/guidelines-surveys/esc-guidelines/about/Pages/rules-writing.aspx).ESCGuide-linesrepresenttheof?cialpositionoftheESConagiventopicandareregularlyupdated.

MembersofthisTaskForcewereselectedbytheESCtorepresentprofessionalsinvolvedwiththemedicalcareofpatientswiththispathology.Selectedexpertsinthe?eldundertookacomprehensivereviewofthepublishedevidenceformanagement(includingdiagno-sis,treatment,preventionandrehabilitation)ofagivenconditionaccordingtoESCCommitteeforPracticeGuidelines(CPG)policy.

Acriticalevaluationofdiagnosticandtherapeuticprocedureswasperformedincludingassessmentoftherisk-bene?t-ratio.Estimatesofexpectedhealthoutcomesforlargerpopulationswereincluded,wheredataexist.Thelevelofevidenceandthestrengthofrecom-mendationofparticularmanagementoptionswereweighedandgradedaccordingtoprede?nedscales,asoutlinedinTables1and2.Theexpertsofthewritingandreviewingpanels?lledindeclara-tionsofinterestformswhichmightbeperceivedasrealorpotential

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sourcesofcon?ictsofinterest.Theseformswerecompiledintoone?leandcanbefoundontheESCWebSite(e43f5da204a1b0717ed5dd2a/guidelines).Anychangesindeclarationsofinterestthatariseduringthewritingperiodmustbenoti?edtotheESCandupdated.TheTaskForcereceiveditsentire?nancialsupportfromtheESCwithoutanyinvolvementfromhealthcareindustry.

TheESCCPGsupervisesandcoordinatesthepreparationofnewGuidelinesproducedbyTaskForces,expertgroupsorconsensuspanels.TheCommitteeisalsoresponsiblefortheendorsementprocessoftheseGuidelines.TheESCGuidelinesundergoextensivereviewbytheCPGandexternalexperts.AfterappropriaterevisionsitisapprovedbyalltheexpertsinvolvedintheTaskForce.The?na-lizeddocumentisapprovedbytheCPGforpublicationintheEuro-peanHeartJournal.Itwasdevelopedaftercarefulconsiderationof

thescienti?candmedicalknowledgeandtheevidenceavailableatthetimeoftheirdating.

ThetaskofdevelopingESCGuidelinescoversnotonlytheintegra-tionofthemostrecentresearch,butalsothecreationofeducationaltoolsandimplementationprogrammesfortherecommendations.Toimplementtheguidelines,condensedpocketguidelinesversions,summaryslides,bookletswithessentialmessages,summarycardsfornon-specialists,electronicversionfordigitalapplications(smart-phonesetc)areproduced.Theseversionsareabridgedand,thus,ifneeded,oneshouldalwaysrefertothefulltextversionwhichisfreelyavailableontheESCWebsite.TheNationalSocietiesoftheESCareencouragedtoendorse,translateandimplementtheESCGuidelines.Implementationprogrammesareneededbecauseithasbeenshownthattheoutcomeofdiseasemaybefavourablyin?uencedbythethoroughapplicationofclinicalrecommendations.Surveysandregistriesareneededtoverifythatreal-lifedailyprac-ticeisinkeepingwithwhatisrecommendedintheguidelines,thuscompletingtheloopbetweenclinicalresearch,writingofguidelines,disseminatingthemandimplementingthemintoclinicalpractice.HealthprofessionalsareencouragedtotaketheESCGuidelinesfullyintoaccountwhenexercisingtheirclinicaljudgmentaswellasinthedeterminationandtheimplementationofpreventive,diag-nosticortherapeuticmedicalstrategies.However,theESCGuide-linesdonotoverrideinanywaywhatsoevertheinpidualresponsibilityofhealthprofessionalstomakeappropriateandac-curatedecisionsinconsiderationofeachpatientshealthconditionandinconsultationwiththatpatientandthepatient’scaregiverwhereappropriateand/ornecessary.Itisalsothehealthprofessio-nal’sresponsibilitytoverifytherulesandregulationsapplicabletodrugsanddevicesatthetimeofprescription.

2.Introduction

ThisdocumentfollowsthetwopreviousESCGuidelinesfocussingonclinicalmanagementofpulmonaryembolism,publishedin2000and2023.Manyrecommendationshaveretainedorreinforcedtheirvalidity;however,newdatahasextendedormodi?edourknowl-edgeinrespectofoptimaldiagnosis,assessmentandtreatmentofpatientswithPE.Themostclinicallyrelevantnewaspectsofthis2023versionascomparedwithitspreviousversionpublishedin2023relateto:

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(1)Recentlyidenti?edpredisposingfactorsforvenousthrombo-

embolism

(2)Simpli?cationofclinicalpredictionrules

(3)Age-adjustedD-dimercut-offs

(4)Sub-segmentalpulmonaryembolism

(5)Incidental,clinicallyunsuspectedpulmonaryembolism

(6)Advancedriskstrati?cationofintermediate-riskpulmonary

embolism

(7)InitiationoftreatmentwithvitaminKantagonists

(8)Treatmentandsecondaryprophylaxisofvenousthrombo-

embolismwiththenewdirectoralanticoagulants

(9)Ef?cacyandsafetyofreperfusiontreatmentforpatientsatinter-

mediaterisk

(10)Earlydischargeandhome(outpatient)treatmentofpulmonary

embolism

(11)Currentdiagnosisandtreatmentofchronicthromboembolic

pulmonaryhypertension

(12)Formalrecommendationsforthemanagementofpulmonary

embolisminpregnancyandofpulmonaryembolisminpatientswithcancer.

Thesenewaspectshavebeenintegratedintopreviousknowledgetosuggestoptimaland—wheneverpossible—objectivelyvalidatedmanagementstrategiesforpatientswithsuspectedorcon?rmedpul-monaryembolism.

Inordertolimitthelengthoftheprintedtext,additionalinforma-tion,tables,?guresandreferencesareavailableaswebaddendaattheESCwebsite(e43f5da204a1b0717ed5dd2a).

2.1Epidemiology

Venousthromboembolism(VTE)encompassesdeepveinthrom-bosis(DVT)andpulmonaryembolism(PE).Itisthethirdmostfre-quentcardiovasculardiseasewithanoverallannualincidenceof100–200per100000inhabitants.1,2VTEmaybelethalintheacutephaseorleadtochronicdiseaseanddisability,3–6butitisalsooftenpreventable.

AcutePEisthemostseriousclinicalpresentationofVTE.SincePEis,inmostcases,theconsequenceofDVT,mostoftheexistingdataonitsepidemiology,riskfactors,andnaturalhistoryarederivedfromstudiesthathaveexaminedVTEasawhole.

TheepidemiologyofPEisdif?culttodeterminebecauseitmayremainasymptomatic,oritsdiagnosismaybeanincidental?nding;2insomecases,the?rstpresentationofPEmaybesuddendeath.7,8Overall,PEisamajorcauseofmortality,morbidity,andhospitaliza-tioninEurope.Asestimatedonthebasisofanepidemiologicalmodel,over317000deathswererelatedtoVTEinsixcountriesoftheEuropeanUnion(withatotalpopulationof454.4million)in2023.2Ofthesecases,34%presentedwithsuddenfatalPEand59%weredeathsresultingfromPEthatremainedundiagnosedduringlife;only7%ofthepatientswhodiedearlywerecorrectlydiag-nosedwithPEbeforedeath.Sincepatientsolderthan40yearsareatincreasedriskcomparedwithyoungerpatientsandtheriskapproxi-matelydoubleswitheachsubsequentdecade,anever-largernumberofpatientsareexpectedtobediagnosedwith(andperhapsdieof)PEinthefuture.9

Inchildren,studiesreportedanannualincidenceofVTEbetween53and57per100000amonghospitalizedpatients,10,11andbetween

1.4and4.9per100000inthecommunityatlarge.12,13

2.2Predisposingfactors

Alistofpredisposing(risk)factorsforVTEisshowninWebAddendaTableI.Thereisanextensivecollectionofpredisposingenvironmen-talandgeneticfactors.VTEisconsideredtobeaconsequenceoftheinteractionbetweenpatient-related—usuallypermanent—riskfactorsandsetting-related—usuallytemporary—riskfactors.VTEisconsideredtobe‘provoked’inthepresenceofatemporaryorre-versibleriskfactor(suchassurgery,trauma,immobilization,preg-nancy,oralcontraceptiveuseorhormonereplacementtherapy)withinthelast6weeksto3monthsbeforediagnosis,14and‘unpro-voked’intheabsencethereof.PEmayalsooccurintheabsenceofanyknownriskfactor.Thepresenceofpersistent—asopposedtomajor,temporary—riskfactorsmayaffectthedecisiononthedur-ationofanticoagulationtherapyaftera?rstepisodeofPE.

Majortrauma,surgery,lowerlimbfracturesandjointreplace-ments,andspinalcordinjury,arestrongprovokingfactorsforVTE.9,15Cancerisawell-recognizedpredisposingfactorforVTE.TheriskofVTEvarieswithdifferenttypesofcancer;16,17haemato-logicalmalignancies,lungcancer,gastrointestinalcancer,pancreaticcancerandbraincancercarrythehighestrisk.18,19Moreover,cancerisastrongriskfactorforall-causemortalityfollowinganepisodeofVTE.20

Infertilewomen,oralcontraceptionisthemostfrequentpredis-posingfactorforVTE.21,22Whenoccurringduringpregnancy,VTEisamajorcauseofmaternalmortality.23Theriskishighestinthethirdtrimesterofpregnancyandoverthe6weeksofthepostpartumperiod,beingupto60timeshigher3monthsafterdelivery,comparedwiththeriskinnon-pregnantwomen.23Invitrofertilizationfurtherincreasestheriskofpregnancy-associatedVTE.Inacross-sectionalstudyderivedfromaSwedishregistry,theoverallriskofPE(com-paredwiththeriskofage-matchedwomenwhose?rstchildwasbornwithoutinvitrofertilization)wasparticularlyincreasedduringthe?rsttrimesterofpregnancy[hazardratio(HR)6.97;95%con?-denceinterval(CI)2.21–21.96].TheabsolutenumberofwomenwhosufferedPEwaslowinbothgroups(3vs.0.4casesper10000pregnanciesduringthe?rsttrimester,and8.1vs.6.0per10000preg-nanciesoverall).24Inpost-menopausalwomenwhoreceivehormonereplacementtherapy,theriskofVTEvarieswidelydepend-ingontheformulationused.25

Infectionhasbeenfoundtobeacommontriggerforhospitaliza-tionforVTE.15,26,27Bloodtransfusionanderythropoiesis-stimulatingagentsarealsoassociatedwithanincreasedriskofVTE.15,28

Inchildren,PEisusuallyassociatedwithDVTandisrarelyunpro-voked.SeriouschronicmedicalconditionsandcentralvenouslinesareconsideredtobelikelytriggersofPE.29

VTEmaybeviewedaspartofthecardiovasculardiseasecon-tinuumandcommonriskfactors—suchascigarettesmoking,obesity,hypercholesterolaemia,hypertensionanddiabetesmelli-tus30–33—aresharedwitharterialdisease,notablyatheroscler-osis.34–37However,atleastinpart,thismaybeanindirectassociation,mediatedbytheeffectsofcoronaryarterydiseaseand,

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inthecaseofsmoking,cancer.38,39MyocardialinfarctionandheartfailureincreasetheriskofPE;40,41conversely,patientswithVTEhaveanincreasedriskofsubsequentmyocardialinfarctionandstroke.42

2.3Naturalhistory

The?rststudiesonthenaturalhistoryofVTEwerecarriedoutinthesettingoforthopaedicsurgeryduringthe1960s.43EvidencecollectedsincethisinitialreporthasshownthatDVTdevelopslessfrequentlyinnon-orthopaedicsurgery.TheriskofVTEishighestduringthe?rsttwopost-operativeweeksbutremainselevatedfortwotothreemonths.Antithromboticprophylaxissigni?cantlyreducestheriskofperioperativeVTE.TheincidenceofVTEisreducedwithincreas-ingdurationofthromboprophylaxisaftermajororthopaedicsurgeryand(toalesserextent)cancersurgery:thisassociationhasnotbeenshownforgeneralsurgery.44,45Themajorityofpatientswithsymp-tomaticDVThaveproximalclots,complicatedbyPEin40–50%ofcases,oftenwithoutclinicalmanifestations.44,45

RegistriesandhospitaldischargedatasetsofunselectedpatientswithPEorVTEyielded30-dayall-causemortalityratesbetween9%and11%,andthree-monthmortalityrangingbetween8.6%and17%.46–48FollowingtheacutePEepisode,resolutionofpulmonarythrombi,asevidencedbylungperfusiondefects,isfrequentlyincom-plete.Inonestudy,lungperfusionscintigraphydemonstratedabnor-malitiesin35%ofpatientsayearafteracutePE,althoughthedegreeofpulmonaryvascularobstructionwas,15%in90%ofthecases.49Tworelativelyrecentcohortstudiescovering173and254patientsyieldedincidencesapproaching30%.50,51Theincidenceofcon?rmedchronicthromboembolicpulmonaryhypertension(CTEPH)afterunprovokedPEiscurrentlyestimatedatapproximately1.5%(withawiderangereportedbymostlysmall-cohortstudies),withmostcasesappearingwithin24monthsoftheindexevent.52,53

TheriskofrecurrenceofVTEhasbeenreviewedindetail.54–56Basedonhistoricaldata,thecumulativeproportionofpatientswithearlyrecurrenceofVTE(onanticoagulanttreatment)amountsto2.0%at2weeks,6.4%at3monthsand8%at6months;morerecent,randomizedanticoagulationtrials(discussedinthesectiononacutephasetreatment)indicatethatrecurrenceratesmayhavedroppedconsiderablyrecently.Therateofrecurrenceishighestduringthe?rsttwoweeksanddeclinesthereafter.Duringtheearlyperiod,activecancerandfailuretorapidlyachievetherapeuticlevelsofanticoagulationappeartoindependentlypredictanincreasedriskofrecurrence.56,57

ThecumulativeproportionofpatientswithlaterecurrenceofVTE(aftersixmonths,andinmostcasesafterdiscontinuationofanticoa-gulation)hasbeenreportedtoreach13%at1year,23%at5years,and30%at10years.56Overall,thefrequencyofrecurrencedoesnotappeartodependontheclinicalpresentation(DVTorPE)ofthe?rstevent,butrecurrentVTEislikelytooccurinthesameclinicalformastheindexepisode(i.e.ifVTErecursafterPE,itwillmostlikelybePEagain).RecurrenceismorefrequentaftermultipleVTEepi-sodesasopposedtoasingleevent,andafterunprovokedVTEasopposedtothepresenceoftemporaryriskfactors,particularlysurgery.58ItisalsomorefrequentinwomenwhocontinuehormoneintakeafteraVTEepisode,andinpatientswhohavesufferedPEorproximalveinthrombosiscomparedtodistal(calf)veinthrombosis.Ontheotherhand,factorsforwhichanindepend-entassociationwithlaterecurrencehavenotbeende?nitelyestab-lishedincludeage,malesex,59,60afamilyhistoryofVTE,andanincreasedbodymassindex.54,56ElevatedD-dimerlevels,eitherduringorafterdiscontinuationofanticoagulation,indicateanincreasedriskofrecurrence;61–63ontheotherhand,singlethrombo-philicdefectshavealowpredictivevalueandanticoagulationmanage-mentbasedonthrombophiliatestinghasnotbeenfoundtoreduceVTErecurrence.64,65

2.4Pathophysiology

AcutePEinterfereswithboththecirculationandgasexchange.Rightventricular(RV)failureduetopressureoverloadisconsideredtheprimarycauseofdeathinseverePE.

Pulmonaryarterypressureincreasesonlyifmorethan30–50%ofthetotalcross-sectionalareaofthepulmonaryarterialbedisoccludedbythromboemboli.66PE-inducedvasoconstriction,mediatedbythereleaseofthromboxaneA2andserotonin,contri-butestotheinitialincreaseinpulmonaryvascularresistanceafterPE,67aneffectthatcanbereve