One-shot diagnostic and prognostic assessment in intermediate- to high-risk acute pulmonary embolism: The role of multidetector computed tomography

Revista

Portuguesa

de

Cardiologia

Portuguese

Journal

of

Cardiology

ORIGINAL

ARTICLE

One-shot

diagnostic

and

prognostic

assessment

in

intermediate-to

high-risk

acute

pulmonary

embolism:

The

role

of

multidetector

computed

tomography

Rui

Baptista

_,

_Inês

_Santiago

_,

_Elisabete

_Jorge

_,

_Rogério

_Teixeira

_,

Paulo

Mendes

_,

_Luís

_Curvo-Semedo

_,

_Grac

_¸a

_Castro

_,

_Pedro

_Monteiro

_,

Filipe

Caseiro-Alves

_,

_Luís

_A.

_Providência

a_{CardiologyUnit,HospitaisdaUniversidadedeCoimbra,CentroHospitalareUniversitáriodeCoimbra,Coimbra,Portugal} b_{FacultyofMedicine,UniversityofCoimbra,Coimbra,Portugal}

c_{RadiologyDepartment,HospitalInfanteD.Pedro,Aveiro,Portugal}

d_{RadiologyUnit,HospitaisdaUniversidadedeCoimbra,CentroHospitalareUniversitáriodeCoimbra,Coimbra,Portugal}

Received17January2012;accepted6May2012 Availableonline11December2012

KEYWORDS Pulmonaryembolism; Prognosis; Rightventricular dysfunction; Thrombolysis; Multidetector computed tomography; Contrast Abstract

Introduction:Contrast-enhancedmultidetectorcomputedtomography(MDCT)isusefulforthe diagnosisofpulmonaryembolism(PE).However,currentguidelinesdonotsupportitsusefor riskassessmentinacutePEpatients.

Objectives: WecomparedtheprognosticimpactofMDCT-derivedindicesregarding medium-term mortalityinapopulation ofintermediate-tohigh-riskPE patients,mostlytreatedby thrombolysis.

Methods:Thirty-nine consecutivepatients admittedtoanintensive careunitwithacutePE werestudied.AllpatientshadapulmonaryMDCTonadmissiontotheemergencyroomaspartof thediagnosticalgorithm.WeassessedthefollowingMDCTvariables:rightventricular/left ven-triculardiameter(RV/LV)ratio,arterialobstructionindex,pulmonaryartery-to-aortadiameter ratioandazygosveindiameter.A33-monthfollow-upwasperformed.

Results:Meanagewas59.1±19.6years,with80%ofpatientsreceivingthrombolysis. Follow-up all-causemortality was 12.8%.Of the MDCT-derivedvariables,only theRV/LV ratio had significantpredictivevalue,beinghigherinpatientswhosufferedtheendpoint(1.6_±0.5vs. 1.9±0.4, p=0.046).Patients with anRV/LV ratio≥1.8had 11-fold highermedium-term all-cause mortality(3.8% vs.38.8%,p<0.001). Regardingthisendpoint,thec-statisticwas 0.78 (95% CI,0.60---0.96) for RV/LV ratio andcalibration was good (goodness-of-fit p=0.594). No otherradiologicalindexwaspredictiveofmortality.

Conclusions: MDCT gives the possibility, in a single imaging procedure, of diagnos-ing and assessing the prognosis of patients with intermediate- to high-risk PE.

∗_{Correspondingauthor.}

E-mailaddress:ruibaptista@gmail.com(R.Baptista).

0870-2551/$–seefrontmatter©2012SociedadePortuguesadeCardiologiaPublishedbyElsevierEspaña,S.L.Allrightsreserved.

Althoughfurtherstudiesareneeded,thesimple-to-calculateRV/LVratiohasgood discrimina-tionandcalibrationforpredictingpooreroutcomesinpatientswithacutePE.

© 2012 Sociedade Portuguesa de Cardiologia Published by Elsevier España, S.L. All rights reserved.

PALAVRAS-CHAVE

Tromboembolia pulmonar; Prognóstico;

Disfunc¸ãoventricular direita;

Trombólise; Tomografia computadorizada; Contraste

Angiografiapulmonarportomografiacomputadorizadaemdoentescom

tromboemboliapumonardemédioaaltorisco:avaliac¸ãodiagnósticaeprognóstica numsóexame

Resumo

Introduc¸ão:Aangiografiapulmonarportomografiacomputadorizadacomcontraste(angio-TC) é recomendadapara odiagnóstico mas não para a estratificac¸ão derisco em doentescom tromboemboliapulmonar(TEP).

Objectivos:Determinar o impacto prognósticoa médio-prazo de vários índicesradiológicos obtidos na angio-TC em doentes com TEP de médio a alto risco, a maioria tratados com fibrinólise.

Métodos: Estudaram-se39 doentesadmitidosnumaunidadedecuidadosintensivos porTEP, todoscomangio-TCpréviarealizadanaurgênciaeseguiram-sedurante33meses.Mediram-se asseguintesvariáveis:razãoentreos diâmetrosdo ventrículodireitoe ventrículoesquerdo (índiceVD/VE),índice deobstruc¸ãoarterial,razãoenteosdiâmetrosdaartériapulmonare aortaediâmetrodaveiaázigos.

Resultados: A idade médiafoi de 59,1_± 19,6 anos; 80% dos doentes foram tratados com fibrinólise.Durante operíododeseguimento clínico,amortalidade foi12,8%.Dasvariáveis analisadas,apenasoíndiceVD/VEdemonstrouvalorpreditivo,sendosignificativamentemais elevadonosdoentesquefaleceram(1,6±0,5versus1,9±0,4,p=0,046).Osdoentescomum índiceVD/VE_≥1,8tiveramumaincidência11 vezessuperiordemortalidadeamédioprazo (3,8%versus38,8%,p<0,001).Relativamenteaesteendpoint,oc-statisticfoide0,78(95%IC 0,60---0,96)eacalibrac¸ãoelevada(goodness-of-fitp=0,594).Nenhumoutroíndiceradiológico demonstrouassociac¸ãocomamortalidade.

Conclusões: Aangio-TCpermitenumúnicoexame,emdoentesdemédioealtorisco, diagnos-ticareestratificaroriscodaTEP.Apesardeseremnecessáriosmaisestudos,oíndiceVD/VE podeidentificardoentescompiorprognósticoapósumaTEP.

© 2012 SociedadePortuguesa de Cardiologia. Publicado por Elsevier España, S.L.Todos os direitosreservados.

Introduction

Pulmonaryembolism(PE)rangesfromasymptomaticforms tolife-threateningmassivearterialpulmonarybed obstruc-tionandmayberesponsibleforupto15%ofallin-hospital deaths.1_{Mortalityis thoughttobecausedinpart byright}

ventricular(RV)pressureoverloadresultinginRVdilatation and dysfunction(RVD), ischemiawith ensuing failureand ultimatelydeath.2

PEcanbedifficult todiagnose andriskstratification is paramount,inordertochoosethebesttherapeuticoption foreachpatient.3,4 _{Contrast-enhancedmultidetector}

com-puted tomography (MDCT) is currently the gold standard fordiagnosing PEandhasagrowing roleinrisk stratifica-tion.Recent evidencehas confirmed thegood correlation betweenechocardiographyandMDCT-derivedindicesofRVD andtheratioofrightventriculartoleftventricular(RV/LV) short-axisdiametershasemergedasthemostaccuratesign ofRVD.5,6_{Also,theextentofPE(thethrombusburdeninthe}

pulmonarybed)hasbeenproposedasanimportant param-eterforpredictingRVDanddeath.7---9_{Atthesametime,the}

numberof patients withlow-risk PE is increasing, due to

thelowerthresholdofclinicalsuspicionandgreater avail-abilityofdiagnostictechniques.10

However,themajority ofstudiesassessing RV/LVratios exclude the most severe patients from MDCT analysis, particularly hemodynamically unstable patients. This is reflected by the low mean RV/LV ratios reported in the literature, ranging from1.15,11 _to1.32.12,13 _Moreover,

theproportionofpatientsundergoingthrombolytictherapy inthesestudieswasalsolow.

Ouraimwastocomparetheprognosticimpactofvarious MDCT-derivedRVD indices onmedium-term mortality in a population ofintermediate-tohigh-riskPEpatients, most ofthemtreatedbythrombolysis.

Methods

Patientpopulation

Weretrospectively studiedallpatients with intermediate-to high-risk PE admitted to the intensive care unit of our department between November 2005 and July 2008. The diagnosis of PE was confirmed by 4- or 64-detector

MDCT in all patients. The clinical severity of pulmonary embolismwasstratifiedusingthesystem proposedby the ESC guidelines.3 _{All patients had intermediate- (positive}

troponin I and/or RV dilatation/dysfunction on echocar-diogram)or high-risk PE(shock, defined by systolicblood pressure<90mmHg).Medicalrecordsofpatientswhowere eligibleforthestudywerereviewedbytwooftheauthors, who were not involved in MDCT reporting. Clinical data was collected prospectively, including demographic, clin-ical, laboratory and echocardiographic data. We assessed a medium-term endpoint of all-cause mortality, and in-hospitalclinicaldeterioration--- acompositeofin-hospital death, need for mechanical ventilation, inotrope usage andrethrombolysis--- wasalsoassessed. Theprotocol was reviewed by the institutional board. The population was divided into two groups, classified by survival status at follow-up(aliveordeceased).

Therapeuticprotocol

Decisions on treatment were the responsibility of the attendingphysician.The indicationsforthrombolytic ther-apy werehypotension, severe hypoxemia,evidence of RV dysfunction on transthoracic echocardiography and evi-denceofsevere pulmonarythrombusburden.Thirty-three (84.6%) patients underwent thrombolysis with alteplase (Actilyse®_{, Boehringer Ingelheim Pharma, Germany)}

fol-lowedbyacontinuousintravenous infusionofheparin.No patientunderwentsurgicalorcatheter-basedembolectomy. Meanfollow-upwasthreeyearsandsurvivalstatuswas avail-ablefor97.4%ofpatients.

Transthoracicechocardiography

Bedside standard two-dimensional echocardiography was performedbytheon-callcardiologistwithaportableAloka®

echocardiographandwasavailablein30patients(77%). Pul-monaryarterysystolicpressure(PASP)wasderivedfromthe rightatrioventricularpressuregradientusingpeakvelocity oftricuspidregurgitationwithcontinuouswaveDopplerin apicalfour-chamberviewandthemodifiedBernoulli equa-tion.Rightatrialpressurewasconsideredequalto5mmHg or10mmHgaccordingtowhetherornottheinferiorvena cavacollapsedduringinspiration,respectively.

Contrast-enhancedmultidetectorcomputed tomography

AllMDCTexaminationswereperformedduringpatientstay in the emergency department by the on-call radiologist. Imageswereobtainedoneithera4-sliceora64-slice multi-detectorCTscannerduringinspiratorybreathholdingwhen possibleorduringquietbreathingifthepatientwasshortof breath.Forpatientsonmechanicalventilation,ventilation was manually suspended in deep inspiration. Intravenous injectionofcontrastmedium (80mlof iodinatedcontrast materialwitha concentrationof 400 mg/ml,at a rateof 3.5---5ml/s)wasstartedusingabolustrackingdevice,when attenuationofbloodinthemainpulmonaryarteryreached

100Hounsfieldunits(HU)forthe4-sliceMDCTand180HU forthe64-sliceMDCTscanners,respectively.

Caudocranial helical acquisition was obtained with a collimation of 0.625---1.25 mm and a pitch of 0.9---1.5. Acquisition time was 0.5 s per rotation and tube cur-rent was modulated between 100 and 700 mA and 100 and 140 kV. The z-axis coverage started 2 cm below the diaphragmandextended uptotheupper partofthe aor-ticarch,enablingvisualizationoftheheartandpulmonary arteriesuptothesubsegmentallevel.Imageswere imme-diatelyanalyzed bytheon-callradiologist, whodiagnosed PE based on the presence of pulmonary arterial filling defects.

Offlineimageanalysis

AllMDCTscanswereretrospectivelyreviewedbytwo inde-pendentradiologists (with 4 and 13 years of experience, respectively) who were blinded to clinical data, results of echocardiography and outcomes. The readers scored pulmonary arterial thrombus load using the system pro-posed by Mastora et al.7 _{The widths of the ventricular}

chambers were evaluated based on a single axial image obtained at the plane of maximal visualization of the ventricular chambers, which was typically at the level of the mitral valve. Axes were measured in diastole on a single transverse scan perpendicular to the long axis of the heart and were defined as the largest distance between the inner aspect of the interventricular septum and the ventricular free wall.14 _{The right ventricle was}

considered dilated if the right ventricular chamber was wider than the left ventricular chamber along the short axis.

Vascular measurements for the diameters of the pul-monaryartery, aorta and azygos vein were also obtained usedadjustedmultiplanarimagesintheplane perpendicu-lartothelongaxisofthevesselbeingconsideredandwere acquired using electronic calipers. The pulmonary artery wasmeasured nearitsbranching,theaortaat themiddle thirdofitsascendingportionandtheazygosveinwhereit facedtherighttrachealwall.

Statisticalanalysis

All variables were tested for normality using the Kolmogorov-Smirnovtest. Ifnormal, values arepresented as mean values ± standard deviation. If the distribution was skewed, values are presented as medians, first and thirdquartiles.Correlations wereanalyzed withthe Pear-son correlation. Results are presented as coefficients of correlation (r). The area under the receiver operating characteristiccurve (AUROC) wasusedfor discrimination; this provides a measure of overall accuracy that is inde-pendentofthedecisioncriterion.Thecriterionvaluewith thehighest accuracy isthe value withtheminimumfalse negativeandfalsepositive resultsat the sametime. Sta-tisticalanalyseswereperformedusingSPSS13.0® _software

(Chicago, Illinois). AUROC analysis was performed using MedCalc® _{software version 6.12 (MedCalc, Mariakerke,}

Table1 Clinicalcharacteristicsandlaboratoryvariablesatinitialdiagnosis.

Total(n=39) Survivors(n=34) Deceased(n=5) p

Age,years 59.1_±19.6 56.0_±19.0 80.3_±3.9 0.001

Bodymassindex,kg/m2 _{29.2±4.2 29.1±4.3 29.8±4 NS}

Meanarterialpressure,mmHg 90.5±13.4 91.9±13.4 81.5±9.9 NS

Heartrate,bpm 97±19.3 97.6±18.8 92.4±24.4 NS O2partialpressure,mmHg 63.8±18.8 64.7±20 58.4±6.9 NS CO2partialpressure,mmHg 32.6±5.7 32.8±5.9 30.9±4.9 NS D-dimers,␮g/l 7.9±6.1 6.8±5.2 16.3±6.8 0.02 Bloodglucose,mg/dl 158.9_±66.6 159.1_±67.6 157.8_±67.1 NS TroponinI,ng/ml 0.2±0.3 0.2±0.3 0.1±0.1 NS eGFR,ml/min/m2 _{71.9±22.9 74.3±22.3 55.7±22.7 NS} C-reactiveprotein,mg/dl 3.9±3.9 4±4.1 3.1±2.1 NS

bpm:beatsperminute;eGFR:estimatedglomerularfiltrationratebytheModificationinDietinRenalDiseaseequation.

Results

Clinicaldata

Atotalof39consecutivepatientsadmittedtoourintensive care unit with an MDCT-confirmed diagnosis of PE were studied. All MDCT parameters were assessable in all patients.BaselinecharacteristicsarepresentedinTable1. Mean age was59.1±19.6years (range22---85 years), with amajority offemales (53.8%).Body massindexwashigh, withameanvalueof29.2±4.2kg/m2_{.Nodifferenceswere}

found in mean blood pressure or heart rate between the groups;similarly,nodifferenceswerefoundbetweengroups regarding arterial blood gases, blood glucose, troponin I, estimatedglomerularfiltrationrateorC-reactiveproteinon admission.D-dimerswerehigherinpatientswhodiedthan insurvivingpatients(16.3±6.8vs.6.8±5.2␮g/l,p=0.02).

ClinicaldataarepresentedinTable2.Mostpatients pre-sentedwithdyspnea(69.2%),followedbychestpain(51.3%). Almost one third suffered syncope (30.8%). The most

commonriskfactorforPEwasrecentmajorsurgery(20.5%), closely followed by neoplasia (17.9%) and a prior throm-boembolic event (17.9%).A typical S1Q3T3 pattern onthe

surfaceECGwasfoundin23.1%ofpatientsandin28.2%right ventricularstrainwaspresent.Thebedsideechocardiogram documentedmean PASPof 56.6±17.0mmHg,withno sig-nificantdifferencesbetweengroups.Regardingtreatment, more than 80% of patients underwent thrombolysis (82.4 vs. 100%, p=0.307). Five percent of these were high-risk patientsaccordingtotheESCguidelines,withhemodynamic instability,while95%wereintheintermediate-riskstratum. Outcomes

There werefive deaths,three of themin-hospital (7.7%). None wasdue to bleeding complications. Median timeto deathwassixdays(range1---40days).Thein-hospital com-bined endpoint ofclinical deteriorationoccurred in 10.3% ofpatients.Duringthethree-yearmedium-termfollow-up, all-causemortalitywas12.8%.

Table2 Symptoms,riskfactorsanddiagnostictestdataatdiagnosis. Total (n=39) Survivors (n=34) Deceased (n=5) p Symptoms,n(%) Dyspnea 27(69.2) 24(70.6) 3(60.0) NS Chestpain 20(51.3) 19(55.9) 1(20.0) NS Cough 4(10.3) 4(11.8) 0(0.0) ---Syncope 12(30.8) 9(26.5) 3(60.0) NS Riskfactors,n(%)

Recentmajorsurgery 8(20.5) 7(20.6) 1(20.0) NS

Neoplasia 7(17.9) 7(20.6) 1(17.9) NS

Priorpulmonaryembolism/DVT 7(17.9) 1(20.6) 0(0.0)

---Diagnostictests,n(%) Electrocardiogram S1Q3T3pattern 9(23.1) 8(23.5) 1(20.0) NS InvertedTwavesinV1---V3 11(28.2) 9(26.5) 2(40.0) NS Echocardiogram PASP,mmHg 56.6±17.0 55.7±15.1 64.0±36.8 NS

Table3 Maincomputertomographypulmonaryangiographyfindings. Total (n=39) Survivors (n=34) Deceased (n=5) p

Arterialobstructionindex 49.4±16.9 49.2±17.9 51.1±8.6 NS

Obstruction≥40%,n(%) 28(71.8) 23(67.6) 5(100.0) NS RVdiameter,cm 5.3±0.8 5.3±0.8 5.3±0.5 NS LVdiameter,cm 3.5±0.9 3.6±0.9 3.1±0.7 NS RV/LVratio 1.7_±0.5 1.6_±0.5 2.0_±0.4 0.046 PAdiameter,cm 3.1±0.4 3.1±0.4 3.2±0.3 NS Aorticdiameter,cm 3.3_±0.5 3.3_±0.5 3.5_±0.1 NS PA/aorticdiameter,cm 0.9±0.2 0.9±0.2 0.9±0.1 NS

Azygosveindiameter,cm 1.1_±0.3 1.1_±0.3 0.9_±0.2 NS

LV:leftventricle;PA:pulmonaryartery;RV:rightventricle.

Quantitativemeasurements

ResultsoftheMDCTvariablesareshowninTable3. Reflect-ing the overall severity of the population, the arterial obstruction indexwasover40% in 71.8%of patients,with ameanof49.4±16.9%.Althoughthisindexcorrelated sig-nificantlywithage,heart rate,troponinIand RV/LVratio (Table4),itwasnotpredictiveofmedium-term mortality. Thishigh arterialobstructionindexwasaccompaniedby a veryhigh mean RV/LV ratioof 1.7±0.5. This variable dif-feredsignificantlybetween thegroups,withhighervalues inpatientswhodiedduringfollow-up(2.0±0.4vs.1.6±0.5, p=0.046).Noneoftheotherradiologicalvariablescorrelated significantlywithmortality.Patientswhounderwent throm-bolysis had similarRV/LV ratios to patients not receiving thrombolysis(1.6±0.7vs.1.7±0.5,p=0.407).

OnAUROCanalysis,thebestRV/LVratiocut-offtopredict medium-termmortalityinthisintermediate-tohigh-riskPE population was1.81, withac-statisticof 0.78(95% confi-denceinterval[CI],0.60---0.96).PatientswithanRV/LVratio ofmorethan1.8had11-foldhighermortalitythanpatients withRV/LVratio<1.8(3.8%vs.38.8%,p<0.001).This com-pares with an established risk marker in PE, troponin I, which,inourpopulation,yieldedac-statisticof0.66(95% CI,0.34---0.97)formedium-termmortality.

Sensitivity and specificity (95% CI) of RV enlargement onMDCTforpredictingdeathduringfollow-upwere80.0% and 76.5%, respectively. Negative and positive predictive values of RV enlargement on MDCT for medium-term all-cause mortality were 96.3% (95% CI, 81.0---99.9%) and 33.3% (95% CI, 9.9---65.1%), respectively. The RV/LV ratio had good calibration (Hosmer-Lemeshow test, p=0.594).

Discussion

The results of our study suggest than in this severelyill, intermediate-tohigh-risk PEpopulation,only RV/LVratio had the ability to predict medium-term mortality. Other radiological parameters, including azygos vein diameter, aortic diameter, pulmonary artery diameter and arterial obstruction index, showed no correlation with the end-point of interest. Analysis of the data on survivors and non-survivorsclearlydemonstratedasignificantdifference inmeanRV/LVratiosbetweenthesegroups.

Follow-upall-causemortalitywas12.8%, similartothe rate seen in larger studies, suggesting that our sample is a representative cohort of PE patients. However, most studiesreportshort-term(usually30---90-day)mortality,11,13

whereaswereportthree-yearfollow-updata.

Althoughechocardiographyhaslongbeenrecognizedas arapid,non-invasiveandsensitivemethodfor demonstrat-ingRVDinacutePEpatients,itisnotroutinelyperformed duetoitslimitedavailabilityinemergencyroomsandpoor imagequalityin some patients. As MDCThasbecome the favoreddiagnostic method in acute PE, itsemergence as adiagnostic tool that can simultaneously risk-stratify the patient is of great value. Arterial obstruction index and RV/LV ratio are the most extensively studied prognostic variablesinpatients withPE.The currentliteratureisnot clearregardingtheassociationofradiologicalindicesofPE severityandmorbidityandmortality,especiallyin predict-inglong-termoutcomes.Moreover,moststudiesonlyinclude patientswithless severeforms of PE,afact thatis high-lighted by the low arterial obstruction and RV/LV indices reported.5,11,12_{TwostudiesfocusedonlyonMDCTfindingsin}

massivePE,usingdifferentdefinitions.Ocaketal.studied

Table4 Correlationsofclinical,laboratoryandechocardiographicdatawithMDCTparameters.

Arterialobstructionindex RV/LVratio

Pearsoncoefficient p Pearsoncoefficient p

Age,years 0.373 0.019 0.353 0.027

Heartrate,bpm 0.432 0.006 0.366 0.022

TroponinI,ng/ml 0.446 0.012 0.315 0.085

PASP,mmHg 0.318 0.106 0.238 0.232

threepatientswithmassivePEandconcludedthatreduced leftatrial and pulmonary vein diameters were important findingsonMDCT.15 _{Limetal.reporteddataon14patients}

with acute massive PE, concluding that MDCT identified patients withright ventricular dysfunctionwith high sen-sitivityand specificity, a finding of relevance in hospitals withoutechocardiographyavailablearoundtheclock.7

Onequestionthatarisesiswhyarterialobstructionindex (or PA thrombus load) wasnot associated withmortality. AlthoughcorrelatedwithtroponinincreaseandRV/LVratio in this intermediate- to high-risk population, it did not predict RVfailure or death. Ourresults are inagreement withthoseofCollomb etal.16 _{andGhayeetal.,}14

suppor-tingtheideathat themostimportantprognosticfactor is howtheRV respondstothe suddenincreasein pulmonary vascularresistanceandnottheextentofthethrombus bur-deninthepulmonarybed.Severalauthorssuggestthatitis uncouplingofRVresourcesfromthepulmonaryarterialload, ratherthanobstruction, thatcausesRVfailure.17,18 _Thisis

furtherevidence that fixed variables, suchas obstruction indexandpulmonarysystolicpressure,areunabletopredict morbidity,astheydonotreflectRV-PAcoupling.Addedto thefactthatcalculationofthearterialobstructionindexis difficultandtime-consuming,theeffectivenessofthisindex intheacutesettingremainstobeproven.

The RV/LV ratio, in contrast, reflects RV volume and pressureoverloadandthus reflectsthepathophysiological processesleadingtoheartfailureanddeath.Leftward shif-ting of the interventricular septum leads to impairment ofleftventriculardistensibilityandpericardialconstraint, limiting left ventricular filling and cardiac output. At the same time, acute RV dilatation aggravates tricuspid regurgitation, itself worsening RV performance. Several reports5,6,14,19,20_{andameta-analysis}13_{suggestthatanRV/LV}

ratio>1.0(or0.9inreconstructedfour-chamberviews)isa strongprognosticmarkerinpatientswithacutePE.Although there is some evidence that reconstructed four-chamber viewsmaybesuperiortoaxialviews fortheidentification of high-risk patients,19 _{several studies have found robust}

prognosticvalueusingstandardaxialacquisitionsto calcu-latetheRV/LVratio.11,12,20

In a large retrospective series of 431 patients, 30-day mortalitywas15.6%inpatientswithRVenlargement (recon-structedfour-chamberviews),definedasRV/LVratio>0.9 onMDCT, comparedto7.7%inthosewithoutthisfinding.6

Intheabove-mentionedmeta-analysisoftwostudies(with twodifferentRV/LV ratiothresholds, 1.5 and1.0) includ-ing 191 normotensive patients with PE, a 58% (95% CI, 51---65%)overallnegativeanda57%positive(95%CI,49---64%) value of RV dilatation were reported on MDCT for pre-dictingearly death, yielding arelative riskfor in-hospital mortality of 2.28 (95% CI, 0.9---5.9).13 _{Our study extends}

thesefindings to a population of severely illpatients (all withRV/LVratio>1.0)anddemonstratesthatpatientswith RV/LV ratio >1.8 have an 11-fold higher risk of mortality during medium-term follow-up. These results are compa-rable to those reported by Ghuysen et al.,14 _{in which}

patientswith amean RV/LVratio of 1.52had amortality of25%.

To date, no study has demonstrated a clear benefit of thrombolysis over an anticoagulation-only strategy in intermediate-riskpatients,3 _{althoughamulticentertrialis}

currently underway toassess thevalue of thrombolysis in thesepatients.21_{Themajorityofourpopulationunderwent}

thrombolysis, due tothe extensive thrombusburden (72% ofpatientswith>50%arterialobstructionindex),severeRV dilatation and elevated markers of myocardialnecrosis in mostpatients.AnelevatedRV/LVratiomayidentifyhigh-risk patientswhowillbenefitmostfromthrombolysis.However, the low positive predictive value of the RV/LV ratio may precludeitsusetojustifytreatmentescalation.

Ourstudyis limitedbyitsretrospective designandthe smallnumberofpatients.Moreover,duetothe character-istics of the population, selected in an emergency room setting,significant heterogeneityamongpatients, particu-larlyregardingcomorbidities,cannotbeexcluded.However, this reflects the actual population referred to our hospi-tal withsuspected or confirmed PE.The echocardiograms werenotperformedbythesameoperatorandhencewedo notprovidequantitativedataonchamberdimensionsorRV function.AlthoughtheMDCTscanswereimmediately inter-pretedbytheon-callradiologist,allexamswerethoroughly reviewedbytworadiologistswhowereblindedtooutcomes andtoechocardiographyresults, whoconfirmedthe diag-nosis ofPEinallpatients.The highusageofthrombolytic therapymayhaveinfluencedthemortalityresults.Noneof theMDCTscanswereECG-gated.

In conclusion, in this selected intermediate- to high-riskPEpopulationwithmarkersofsevererightventricular dysfunction,most of whomwere treatedwith thromboly-sis, only the MDCT-derived RV/LV ratio was predictive of medium-term death. Regular reporting of this parameter by the radiologist, jointly with the diagnosis of PE, may helptheattendingphysiciantorisk-stratifyPEpatients.

Ethical

disclosures

Protection of human and animal subjects.The authors declarethatnoexperimentswereperformedonhumansor animalsforthisstudy.

Confidentialityofdata.Theauthorsdeclarethattheyhave followedtheprotocolsoftheirworkcenteronthe publica-tionofpatientdataandthatallthepatientsincludedinthe studyreceivedsufficientinformationandgavetheirwritten informedconsenttoparticipateinthestudy.

Right to privacy and informed consent.The authors declarethatnopatientdataappearinthisarticle.

Conflicts

of

interest

Theauthorshavenoconflictsofinteresttodeclare.

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