Embolia polmonare: ciò che le linee guida non dicono polmonare: ciò che le linee guida non dicono...

Emboliapolmonare:ciòchelelineeguidanondicono

F.Numeroso,UOProntoSoccorsoeMedicinad'UrgenzaAziendaOspedaliero-UniversitariadiParma

TEP,CIO’CHELEGLNONDICONO:MACOSANONDICONO?

TEP,CIO’CHELEGLNONDICONO:FONTIBIBLIOGRAFICHE

Ø Growingevidencesuggestingover-diagnosisofPE

Ø Diagnosticvalueandclinicalsignificanceofsub-segmentaldefects

Ø Incidental(unsuspected)PE

Ø Triplerule-out’CTangiographyforpatientswithchestpain

Ø Roleofreduced-doseiv.thrombolysis,catheter-directedtreatmentinintermediate-riskpatients

Ø UseofneworalanticoagulantsinthetreatmentofPEandsecondarypreventionofVTE

Ø Criteriaforearlydischargeandhometreatmentoflow-riskpatients

Ø Roleofmagneticresonanceimaging

Ø VTEinpregrancy

Ø Optimalmanagementofpatientswithcancer

Ø Follow-upafterPE:durationofanticoagulationandsearchCTPvasculardisease

TEP,CIO’CHELEGLNONDICONO:MACOSANONDICONO?

(ESCGL2014,JACC2016)

TEP,CIO’CHELEGLNONDICONO:OVERDIAGNOSISOFPE

• To compare incidence, mortality and treatment complications (GI tract or intracranialhemorrage or secondary thrombocytopenia) of PE before and after CTPAwas introduced

TEP,CIO’CHELEGLNONDICONO:OVERDIAGNOSISOFPE

• PEisthequintessentialdiagnosisofmedicinebecouse itcapturesallthecomplexityofmedicinein

theevidence-basedera

• Thefactthatdeathratesremainstablewhereasincidencehasnearlydoubledsuggeststhatnearly

halfofthepts.diagnosedashavingPEexperienceonlytherisksoftherapywithout thebenefit

• Therearestrikinggapsinourknowledge.Whatevidencesupports anticoagulation?AreallPES

equallyconcerning?Whatisthenumberneededtotreattopreventerecurrenceordeath?

• Industry-sponsored studiescontinuestotesttrivialities.Instead,fundamentalquestionmustbe

answered.WichpatientwithVTEbenefitfromanticoagulationatall?

Arch Intern Med. 2012

TEP,CIO’CHELEGLNONDICONO:GESTIONETEPSUBSEGMENTARIA

• Difetti di riempimento a carico di arteriole di 2-3 mm di diametro

• Incidenza: 4.7-15% among positive CTPAs

• Bassa specificità CT (37-46%), scarso accordo inter-osservatori (51%)

• Il dolore toracico è il sintomo più comune ma spesso il riscontro è occasionale

• Rispetto ai casi di TEP prossimale: maggiori livelli di PaO2 e spO2, DVT meno

frequente, biomarcatori più bassi (ddimero), meno frequenti alterazioni ECG,

solitamente stabilità emodinamica e assenza di disfunzioneVDx


Methods:Weanalyzed3728consecutivepatientswithclinically suspectedPE. SSPEpatientswerecontrastedtopatientswithmoreproximalPEandtopatientsinwhomsuspectedPEwasruledout,inregardsoftheprevalenceofthromboembolicriskfactorsandthe3-monthrisksofrecurrentvenousthromboembolism(VTE)andmortalityResults:PatientswithSSPEappeartomimic thosewithmoreproximally locatedPEregardingtheirVTEriskprofileandclinical outcome.

Prognosi

Aim:toestablishwhethertheincidence ofrecurrentVTEandmortalityisloweramongpatientswithisolatedSSPEwhoaretreatedwithanticoagulanttherapycomparedwiththosewhoarenottreatedwithanticoagulanttherapyMethods:Weidentifiedsix observational studies,withonlyasmallnumberofpatientswithSSPE nottreatedwithanticoagulantsResults:Atotalof47patientsmetthosecriteria,ofwhomnonediedandnonedevelopedrecurrentvenousthromboembolismwithin3months


POSIZIONE DELLE LINEE GUIDA

Ø ESC Guidelines, 2014

• “The diagnostic value and clinical significance of sub-segmental defects on MDCT are

still under debate”

• “The definition of sub-segmental PE has yet to be standardized”

• “Further testing to confirm PE may be considered in case of isolated sub-segmental

clots (2b C)»

• “In a patient with isolated sub-segmental PE and non proximal DVT, the decision on

whether to treat should be made on an individual basis, taking into account the

clinical probability and the bleeding risk”



Ø ACCPGuidelines2012:questionnotaddressed

Ø ACCPGuidelines,Update2016

• “Becausetheabnormalitiesaresmall,adiagnosisofsubsegmentalPEismorelikelytobe

false-positivefindingthanadiagnosisofPEinthesegmentalormoreproximalpulmonary

arteries”

• “BecauseatruesubsegmentalPEislikelytohavearisenfromasmallDVT,theriskof

progressiveorrecurrentVTEwithoutanticoagulationisexpectedtobelowerthanin

patientswithalargerPE”

• “ForsubsegmentalPEandnoproximalDVT,wesuggestclinicalsurveillanceover

anticoagulationwithalowriskofrecurrentVTE(Grade2C),andanticoagulationover clinical

surveillancewithahighrisk(Grade2C) ”

TEP,CIO’CHELEGLNONDICONO:GESTIONETEPINCIDENTALE

• PEsilenticlinicamente,individuateinmanierainattesa,pre- opost-mortem

• NettoincrementodellafrequenzadopointroduzionediscannerCTmultidetector

• Interessanoarterielobariosegmentalimaanchesubsegmentalietalvolta“acavaliere”

• Circalametàdeicasisonoindividuatisolodallarivalutazionedelleimmagini(radiologi

nonpreparatiacercarli,lesionidistraenti,piccoledimensioni)

• Riportatainpazientioncologici(1-5%)maanchenononcologici,contrauma,patologie

polmonariacute,sottopostiaventilazionemeccanicaoinautopsiepost-mortem

• Perdefinizioneinsospettaticlinicamentemapoiconrivalutazioneanamnesticamirata

sintomiosegninel44-75%,secondoalcuniautori

Tex Heart Inst J. 2013; 40(1): 9–12.

Thrombosis Research 2016: 138: 55–60

• Ignota la storia naturale, varia con quella della malattia di base

• Dati contrastanti sul ruolo prognostico (mortalità e morbosità)

• Non definita la gestione terapeutica, anche se

! frequenti in autopsie e generalmente non contribuivano al decesso

! casi misconosciuti alla prima diagnosi e per questo non trattati non sono

risultati associati a prognosi avversa

• In assenza di dati sull’efficacia del trattamento, nella maggior parte dei casi

vengono gestiti al pari delle embolie sintomatiche e come tali trattate


Tex Heart Inst J. 2013; 40(1): 9–12.




• Someexpertsbelievethatpatientswithincidental(unsuspected)PEonCTshouldbe

treated,especiallyiftheyhavecancerandaproximalclot,butsolidevidencein

supportofthisecommendationislacking.

• Theirsignificance,particularlyiflimitedtosegmentalorsub-segmentalarteries,is

unclear;however,inviewofthehighriskofanadverseoutcomereportedby

uncontrolledstudies,thetreatmentstrategiesrecommendedforsymptomaticPE

shouldbealsoconsideredforincidentalPEfoundinpatientswithmalignancy

• IncidentalPEinpatientswithcancershouldbemanagedinthesamemanneras

symptomaticPE.(gradeIIaC)

POSIZIONEDELLELINEEGUIDA

Ø ACCPGuidelines2012

• InpatientswhoareincidentallyfoundtohaveasymptomaticPE,we

suggestthesameinitialandlong-termanticoagulationasforcomparable

patientswithsymptomaticPE(grade2B)


TEP,CIO’CHELEGLNONDICONO:DIFFICOLTA’DIAGNOSTICHE

ACCURATEZZACTA- Sensibilità =83%- Specificità=96%- VPP=86%- VPN=95%

Conclusion: The predictive value of either CTA or CTA–CTV is high with a concordant

clinical assessment, but additional testing is necessary when clinical probability is

inconsistent with the imaging results.


• PIOPED II investigators recommend stratification of all patients with suspected PEaccording to an objective probability assessment. In patients with discordant findings onclinical assessment and CT imaging, further evaluation depends on clinical judgment


Technical

Breathing

Rippling

Bolus-related

Streakartifacts

Windowssetting

Anatomical

Volumeaveragingartifacts

Vessel orientation

Bronchovascularanatomy

Lymphnodesandperibronchovasculartissue

Mucous-filledbronchus

Patient-related

Obesity

Pulmonarydieases

Vascularvasoconstriction

Arteryobstructionduetoextrinsiccompression

Pulmonaryarterialcatheters

PitfallsinCTdiagnosisofacutePE

SeminarsinRoentgenology,2015


Aim:ToquestiontheconventionaltheorythatPEareabnormalandtotestthehypothesisthatsmallperipheralPEareafunctionoflife

Methods:Thestudygroupincluded26womenand24menwithPEandalower-extremityvenousUSperformedwithin7daysoftheCT.ThelocationsofthePEwereplottedonapulmonaryarterialdiagram,andwidthofthemostproximalclotforeachpatientwasmeasured

Results:33(66%)patientshadPEinthecentralpulmonaryarteries,ofwhich19(58%)hadDVT.17(34%)patientshadperipheralPE;DVTwasdetected in0(0%)patients.Theperipheral clotsmeasured1.0–3.8mm(mean2.5mm),theyappearedfocalandroundedwitha“dotlike”appearance.

Conclusion:Peripheral,focalfillingdefectsinthepulmonaryarteries,whichwetermed“dots,”arenottraditionalembolicclots,arenotassociatedwithdetectable lower-extremityclot loadandmayrepresent“normal”embolicactivityoriginating fromthelowerextremityvenousvalvesinaphysiologicprocesswiththelungcapillary bedstrappinganddissolvingtheembolibyendogenousfibrinolysis,therebyprotectingthesistemiccirculation

TEP,CIO’CHELEGLNONDICONO:QUANDOCERCAREUNATEP?

• “Fishing” is rampant. By fishing, I mean scanning the body part thought to be the source of the

patient's complaint or problem, hoping thereby to reel in some sort of diagnosis. This sport

typically takes place in the emergency department

• In this scenario, a primary diagnosis of PE occasionally turns out to be right. Much more

commonly, however, critical review of the pre-test evidence clearly points to a different diagnosis

that could and should have been made presentation Nevertheless once these defects are

detected all thinking stops and anticoagulation automatically ensues

• I wonder how many normal, asymptomatic volunteers would have filling defects in their

pulmonary arteries if they were to undergo conventional pulmonary arteriography or contrast-

enhanced multidetector chest CTTex Heart Inst J. 2013; 40(1): 9–12.


AmericanCollegeofChestPhysicians&AmericanThoracicSociety,2013

FiveThingsPhysiciansandPatientsShouldQuestion

Radiology,2007


In caso di TVP: SI'!

AIM:Todetermine,bysystematicreviewoftheliterature, theprevalenceofsilentPEinpatientswithdeepvenousthrombosisRESULTS:SilentPEwasdiagnosedin1665of5233patients(32%)withdeepvenousthrombosis.Theincidence ofsilentPEwashigherwithproximaldeepvenousthrombosisthanwithdistaldeepvenousthrombosis.SilentPEseemedtoincreasetheriskofrecurrentPE:25of488(5.1%)withversus7of1093(0.6%)withoutsilentPE


In caso di TVP: NO!

Methods:Aprospectiveandconsecutiveassessmentof103hospitalizedpatientswithlowerlimb

DVTintheabsenceofPEsymptoms,usingCTscan.D-dimerwasquantifiedbefore

anticoagulation.

Results: Theincidence ofS-PEwas66%.In77%ofthesecases,themainandlobarpulmonary

arterieswereaffected.IliacandfemoralDVTsmostoftenproducedS-PE.Diagnosisentailedhigher

hospitalizationexpenses.Nosignificant recurrence rateofthromboticeventswasobservedinthe

S-PEgroupduringthefollow-up.

Conclusions:Theincidence ofS-PEinlower-limbDVTishigh,butintheabsenceofsymptoms,

diagnosisdoesnotappeartobenecessary,astherearenoshort- orlong-termclinical or

therapeuticconsequences.

In caso di TVP: SI’, MA SOLO IN ALCUNE OCCASIONI


Purpose: The purpose of this investigationwas to determine the prevalence of silent PE in

patients with deep venous thrombosis (DVT) limited to the calf veins.

Results: The prevalence of silent PE in patients with DVT limited to the calf veins was

described in 6 investigations. Pooled data showed a prevalence of 24 of 183 (13.1%)

Conclusion: Silent PE in patients with DVT limited to the calf veins is not rare. Imaging at

the time of diagnosis of calf vein DVT, typically with a perfusion scan alone, may be useful,

but there is an economic cost and exposure to radiation.

TEP,CIO’CHELEGLNONDICONO:RISOLUZIONEDELTROMBOEOSTRUZIONERESIDUA

Objective:little isknownaboutthechangesinclotburdenthatoccuratthelevelofthepulmonaryarteriesafterdocumentedPEDesign:systematicanalysisofstudiesofimagingtests(radionuclideandCT)evaluatingresolution rateofPEResults:Thepercentageofpatientswithresidualpulmonarythrombiwas87%at8daysafterdiagnosis,68%after6weeks,65%after3months,57%after6months,and52%after11months.Discussion:Physiciansshouldbeawareofthehighpercentageofincomplete resolutionofpulmonaryemboli(>50%after6months).Routinere-imagingaftercessationofanticoagulanttherapytoobtainanewbaselinecouldbeconsidered


Fonte Fattorepredittivo

AmJRoentgenol,2010 Calibrodellearteriecoinvolte(primase>)

InternEmergMed,2011 Età;coesistentepneumopatia

EurJInternMed,2012 Burdentromboticoiniziale;alterazioneemogasanalitica;precedentiepisodi diTVE

AmJRoentgenol,2013 Calibrodellearteriecoinvolte(primase<)

BloodCoagulFibrinolysis, 2015 Dimensionedell’embolo

Risoluzionedeltrombo:fattoripredittivi


Aim: to investigate the rate of clot resolutionover time and identify risk factors of residualemboli in PE patientsMethods: We retrospectively analyzed 764 PEpatients with follow-up CT scans between day 3and 90. They were classified into 3 cohorts,based on the time of scan: day 3–7, 8–21, 22–90Results: The rate of complete resolution ofpulmonary emboli was 24% at 3–7 days, 47% at8–21 days and 78% at 22–90 days. Regardless ofthe time interval, larger pulmonary arteryinvolvement was only independent predictor ofresidual emboli. The presence of residual emboliwas not associated with an adverse outcome ofPE and rate of VTE recurrence

Aim: to assess the impact of RPO on the

development of recurrent symptomatic

VTE episodes and/or CTPH

Methods: The long-term follow-up was

obtained in 16 patients with and in 89

without RPO.

Results: We did not find any correlation

between RPO, assessed by CT scanning six

months after PE, and the development of

late complications



Ø ESCGuidelines, 2014

Chronic thromboembolic pulmonaryhypertension is a debilitating disease causedby chronic obstruction of major pulmonaryarteries. CTPH has been reported to be along-term complication of PE, with areported cumulative incidence of 0.1–9.1%within the first two years after asymptomatic PE event

TEP,CIO’CHELEGLNONDICONO:DIMISSIONEPRECOCE

Chest 2016 Feb 18

ActualmanagementofPE



Ø ACCPGuidelines,2012


Ø ACCP Guidelines, Update 2016


Evidenzedisponibiliinletteratura

TEP,CIO’CHELEGLNONDICONO: DIMISSIONEPRECOCE


Introduction:StudiesofoutpatientcareafterPEwererestrictedbysmall samplesizes,retrospectivedesignsandtheabsenceofarandomisedcontrolgroupforcomparisonwithinpatientcareMethods344patientswithacute,symptomaticPEalowriskofdeath(PESIriskclasses IorII)assignedtoinitialoutpatient(discharged≤24h)orinpatient treatmentwithsubcutaneousenoxaparin(≥5days)followedbyoralanticoagulation (≥90days).Theprimaryoutcomewassymptomatic,recurrentVTEwithin90days;safetyoutcomesincludedmajorbleedingwithin14or90daysandmortalitywithin90days.Findings 1(0,6%)of171outpatientsdevelopedrecurrentvenousthromboembolismwithin90dayscomparedwithnoneof168inpatient.Only1(0,6%)patientineach treatmentgroupdiedwithin90days,and2(1,2%)of171outpatientsandnoinpatientshadmajorbleedingwithin14days.By90days,3(1,8%)outpatientsbutnoinpatientshaddevelopedmajorbleedingMeanlengthofstaywas0,5daysforoutpatientsand3,9daysforinpatients.InterpretationInselected low-riskpatientswithPE,outpatientcarecansafelyandeffectivelybeusedinplaceofinpatientcare


Lastratificazionedelrischio

Rulesbasedonasamplesetofclinical criteria

Erkens,2010;Kovacs,2010;Zondag,2010;Davies,2007;Rodriguez-Cerrillo,2009;Wells,2005

Parameters as:SBP,spO2,age>18,CrCl>30Clinicalconditionsas:nocontroindicationsforEPWH,nocomorbidities,noneedforparenteralnarcotics,nohighriskforhemorrage,noneedfortrombolysis,nopregnancy,noHF,norenalorliverimpairment,patientcompliance

Prognosticrulesbasedonclinical findings

PESI,2005 Variables:age;malegender;cancer; HF;COPD;HR>110;SBP<100;RR>30breaths/min;T<36C°;alteredmental status;spO2<90%

SimplifiedPESI,2010 Variables:age>80;cancer;HForCOPD;HR>110;SBP<100;spO2<90%

Spanishscore,2007 Variables:severebleeding;cancer;serumCr>2mg/dL; immobilization,nosurgeryinthepast2months,age>60

Geneva,2000 Variables:cancer;previousDVT;HF;SBP<100;DVTshownbyUS;PaO2<8.5kPa

Prognosticrulescombiningclinical data,biomarkersandimagingdata

ESCscore,2014 Variables:shockorhypotension;PESIIIIorIV; signsofRVdysfunction;biomarkers

LR-PEDscore,2012 Variables:age;chronicHF;AF;HR;troponinI;creatinin;glucoselevel;PCR

PREPscore,2010 Variables:cancer;cardiacorrespiratorydiseases; cardiogenicshock;alteredmentalstatus;BNP;righttoleftventriclediameterratio

PROTECT Variables:sPESI;troponinI;BNP;lowerlimbUS

FAST Variables:H-FABP;HR;syncope

Journal ofThrombosis andHaemostasis, 2015Journal ofThrombosis andHaemostasis, 2015

TEP,CIO’CHELEGLNONDICONO:CONCLUSIONI

l L’utilizzo di esami strumentali molto sensibili e di procedimenti diagnostici

spesso non basati sulla PPT comporta il rischio di overdiagnosis ed il

crescente riscontro di casi di PE subsegmentale o incidentale né è la

conferma. Nella quasi totalità di questi casi viene intrapresa terapia

anticoagulante ma questa è una pratica non basata sull’evidenza. Vi è uno

stringente bisogno di LG che consentano di selezionare pazienti a basso

rischio da destinare a regime di sola osservazione clinica, risparmiando i

rischi legati al trattamento. Diversamente i medici continueranno a

prescrivere terapia anticoagulante, anchepermotivi medico-legali

§ Non conoscendo in modo chiaro i meccanismi che presiedono alla

completa risoluzione del trombo né il suo significato prognostico, non

sembra giustificata la ripetizione sistematica di TC per ricerca di una

ostruzione vascolare residuamediante esami strumentali

§ Per identificare i pazienti a rischio per CTPH, sembra ragionevole

seguire l’iter suggerito dalle GL ESC (sospetto clinico > ECO > V/P scan

> conferma con angiografia, TC o RMN)


§ Nel corso degli ultimi anni si è assistito ad una riduzione della durata

della degenza per PE anche se, almeno in Europa, l'ospedalizzazione

resta ancora mediamente prolungata (9-10 gg) ma non tutte le PE

sono uguali e talvolta in caso di pazienti a basso rischio appare

possibile una dimissione precoce

§ L'esecuzione di RCT da cui provengano evidenze forti nonché, forse,

l'utilizzo dei NAO potrebbero ottimizzare la gestione dei pazienti con

PE consentendo dimissione precoce dei pazienti a basso rischio con

notevole risparmio di risorse


Grazieperl’attenzione!!

TEP,CIO’CHELEGLNONDICONO

Embolia polmonare: ciò che le linee guida non dicono polmonare: ciò che le linee guida non dicono...

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