Italian registry of cardiac magnetic resonance.

ContentslistsavailableatScienceDirect

European

Journal

of

Radiology

j ou rn a l h om ep a g e :w w w . e l s e v i e r . c o m / l o c a t e / e j r a d

Italian

registry

of

cardiac

magnetic

resonance

Marco

Francone

_,

_Ernesto

_Di

_Cesare

_,

_Filippo

_Cademartiri

_,

_Gianluca

_Pontone

_,

Luigi

Lovato

_,

_Gildo

_Matta

_,

_Francesco

_Secchi

_,

_Erica

_Maffei

_,

_Silvia

_Pradella

_,

Iacopo

Carbone

_,

_Riccardo

_Marano

_,

_Lorenzo

_Bacigalupo

_,

_Elisabetta

_Chiodi

_,

Rocco

Donato

_,

_Stefano

_Sbarbati

_,

_Francesco

_De

_Cobelli

_,

_Paolo

_di

_Renzi

_,

and

CMR

Italian

Registry

Group,

Guido

Ligabue

_,

_Andrea

_Mancini

_,

_Francesco

_Palmieri

_,

Gennaro

Restaino

_,

_Giovanni

_Puppini

_,

_Maurizio

_Centonze

_,

_Wiliam

_Toscano

_,

Carlo

Tessa

_,

_Riccardo

_Faletti

_,

_Massimo

_Conti

_,

_Arnaldo

_Scardapane

_,

_Salvatore

_Galea

_,

Carlo

Liguori

_,

_Marzio

_Pagliacci

_,

_Domenico

_Lumia

_,

_Marco

_di

_Girolamo

_,

Andrea

Romagnoli

_,

_Alessandro

_Guarise

_,

_Stefano

_Cirillo

_,

_Biagio

_Gagliardi

_,

Claudia

Borghi

_,

_Matteo

_Quarenghi

_,

_Franco

_Contin

_,

_Fiorenzo

_Scaranello

_,

Armando

Tartaro

_,

_Carlo

_Marinucci

_,

_Lorenzo

_Monti

a_{DepartmentofRadiological,OncologicalandPathologicalSciences,SapienzaUniversityofRome,Italy} b_{DipartimentodiScienzeClinicheApplicateeBiotecnologie,UniversitàdiL’Aquila,Italy}

c_{Cardio-VascularImagingUnit,GiovanniXXIIIHospital,MonastierdiTreviso,TV,Italy} d_{ErasmusMedicalCenterUniversity,Rotterdam,TheNetherlands}

e_{IRCCSCentroCardiologicoMonzino,Italy} f_{PoliclinicoS.OrsolaBologna,Italy} g_{AziendaospedalieraGBrotzuCagliari,Italy}

h_{IRCCSPoliclinicoSanDonato,RadiologyUnit,Milan,Italy} i_{AziendaOspedalieraUniversitariaCareggi,Italy} j_{PoliclinicoGemelli,UniversitàCattolicaRoma,Italy} k_{OspedaleGalliera,Genova,Italy}

l_{OspedaleS.AnnaFerrara,Italy}

m_{AziendaOspedalieraUniversitariaG.Martino,Me,Italy} n_{OspedaleMadreGiuseppinaVannini,Roma,Italy} o_{IRCCSS.Raffaele,UniversitàVitaSalute,Milano,Italy} p_{FateBeneFratelliIsolatiberina,Roma,Italy}

q_{AziendaOspedaliera-UniversitariaPoliclinicodiModena,Italy}

r_{DiparimentodiDiagnosticaperimmaginieradiologiainterventistica,OspedaleS.MariadelleGrazie,Pozzuoli,Napoli,Italy} s_{UniversitàCattolicaCampobasso,Italy}

t_{UOCRadiologia,PoloChirurgicoConfortini,AziendaOspedalieraUniversitariaIntegrataVerona,Italy} u_{RadiologiaOCS.ChiaraTrento,Italy}

v_{UOCdiRadiologiaOspCattinaraTrieste,Italy} w_{OspedaleVeriliaCaMaioreLucca,Italy} x_{RadiologiauniversitàTorino,Italy}

y_{Cardiologia-RadiologiaGuastallaAUSLReggioEmilia,Italy} z_{UOCdiRadiodiagnosticaUniversitariaBari,Italy} aa_{OspedaleLameziaTerme.ASPCatanzaro,Italy}

ab_{AreadiDiagnosticaperImmagini,UniversitàCampusBiomedicoRoma,Italy} ac_{OspedaleInfermiRimini,Italy}

ad_{OspedalediCircoloFondazioneMacchi-UniversitàdegliStudidell’InsubriaVarese,Italy} ae_{Università“Sapienza”RadiologiaA.O.Sant’AndreaRoma,Italy}

Abbreviations:CAD,coronaryarterydisease;CMP,cardiomyopathy;CMR,cardiacmagneticresonance;SIRM,ItalianSocietyofMedicalRadiology. ∗ Correspondingauthorat:UniversitàdiL’Aquila,ViaVetoio1,67100L’Aquila,Italy.Tel.:+390862368306;fax:+390862369797.

E-mailaddress:ernesto.dicesare@cc.univaq.it(E.DiCesare).

1 _{Theseauthorscontributedequallytothiswork.}

0720-048X/$–seefrontmatter © 2013 Elsevier Ireland Ltd. All rights reserved.

af_{PoliclinicoUniversitarioTorVergataRoma,Italy} ag_{BassanoDelGrappaVicenza,Italy}

ah_{OspedaleMaurizianoUmbertoITorino,Italy} ai_{AziendaospedalieraGMoscatiAvellino,Italy} aj_{RadiologiaOspedaleValduce,Como,Italy} ak_{Policlinico,Monza,Italy}

al_{AltoVicentinoThieneSchio,Italy}

am_{OspedaleS.MariadellaMisericordiaRovigo,Italy}

an_{IstitutoTecnologieAvanzateBiomedicheUniversitàChieti-Pescara,Italy} ao_{OspedaleMazzoniAscoliPiceno,Italy}

ap_{IRCCSIstitutoClinicoHumanitas,RozzanoMilano,Italy}

a

r

t

i

c

l

e

i

n

f

o

Articlehistory: Received25March2013 Receivedinrevisedform 11September2013 Accepted9October2013 Keywords: CMR-registry Clinicalindications Safetyprofile Acquisitionprotocols Patient’smanagement

a

b

s

t

r

a

c

t

Objectives:Fortysiteswereinvolvedinthismulticenterandmultivendorregistry,whichsoughtto eval-uateindications,spectrumofprotocols,impactonclinicaldecisionmakingandsafetyprofileofcardiac magneticresonance(CMR).

Materialsandmethods:Datawereprospectivelycollectedona6-monthperiodandincluded3376patients (47.2±19years;range1–92years).Recruitedcenterswereaskedtocompleteapreliminarygeneral reportfollowedbyasingleform/patient.Referralphysicianswerenotrequiredtoexhibitanyspecific certificateofcompetencyinCMRimaging.

Results:Examswereperformedwith1.5Tscannersin96%ofcasesfollowedby3T(3%)and1T(1%) magnetsandcontrastwasadministeredin84%ofcases.Themajorityofcaseswereperformedforthe workupofinflammatoryheartdisease/cardiomyopathiesrepresentingoverall55.7%ofexamsfollowed bytheassessmentofmyocardialviabilityandacuteinfarction(respectively6.9%and5.9%ofpatients).

In49%ofcasesthefinaldiagnosisprovidedwasconsideredrelevantandwithimpactonpatient’s clinical/therapeuticmanagement.Safetyevaluationrevealed30(0.88%)clinicalevents,mostofwhich duetopatient’spreexistingconditions.Radiologicalreportingwasrecordedin73%ofexams.

Conclusions:CMRisperformedinalargenumberofcentersinItalywithrelevantimpactonclinical decisionmakingandhighsafetyprofile.

© 2013 Elsevier Ireland Ltd. All rights reserved.

1. Introduction

CMRhasevolved inrecent years froman effectiveresearch tool into a clinically proven, safe and comprehensive imaging modality,withestablishedguidelinesandappropriateness crite-ria covering a wide spectrum of clinical indications and an increasing number of centers organizing fully dedicated scan-ning sessions being carried out either by radiologists and/or cardiologists[1,2].Mostinformationaboutitsuseanddiagnostic performanceshowever,iscurrentlyderivedfromveryfewlarge clinicaltrialsorfromselectedpopulationsenrolledinhighly spe-cializedcenterswithrelativelylimitedknowledgeofitsday-to-day utilization.

TheonlyavailableregisteristheEuroCMR,whichwasrecently completed with 27,000 patients and was promoted and orga-nizedby theEuropeanSocietyof CardiologyWorking Groupof “CardiovascularMagneticResonance”,withobviouspredominant involvementofCMR-dedicatedcardiologicalcenters[3–5]

EuroCMR results convincingly showed that the exam has evolvedfrom thestatus of “aniche modality” [6]with limited numberofcasesperformedbyfewtertiary/academicreferralinto aroutineimagingmodality,homogeneouslydiffusedand repre-sentinganextremelyvaluablediagnosticsupporttosolvecommon clinicalproblems[3,4].

TheItalianregistryofCMRisanopen-accessstudy(no restric-tion criteria or proof of specific competence were required to participating centers) which was set up to provide a national overviewofitsutilization,offeringamore“radiological”pointof viewofitscurrentclinicalroleindailypractice,andwaspromoted bythesub-societyofcardiacradiologyofSIRM(SocietàItaliana diRadiologiaMedica),whichhascurrentlyalmost700members (www.sirm.org/sottositi/cardio).

Fortydifferentcenterswereinvolvedinthismulticenter and multivendorregistry,whichsoughttoevaluateclinicalindications, spectrum of acquisition protocols, impact on clinical decision-makingandsafetyprofileofCMR.

2. Materialsandmethods

2.1. Datacollection

Thedatawereprospectivelycollectedduringa6-monthperiod (January–June2011)andincludedapopulationof3376consecutive patientswhounderwentCMRinoneofthe40participatingsites.

Centerswereinitiallyrecruitedviaemailfromthemailinglist oftheSIRMmembers(approximately8000members)and each site,afteracceptance,appointeda referralphysician(radiologist orcardiologist)whowaslocallyresponsibleforthedataintegrity, interpretationandcollectionandrepresentedthedirectcontactfor thesteeringcommitteeofthestudy.

Referralphysicians werenotrequiredtoexhibitanyspecific sub-specialtybasedcertificateofcompetencyinCMRimagingas theaimofpresentregistrywastoprovidearealistic“snapshot”of CMRutilizationinItaly,withoutlimitingpatient’senrollmentonly tomost-experiencednationalgroups.

Similarly,acquisitionprotocolswereindividuallydefinedand tailoredbyeachcenteraccordingtothemainclinicalrequest, with-outfollowinganyestablished,predefinedstandardizedprotocol. 2.2. Patientsform

Apreliminarygeneralreportandacase-reportform(CRF)were completedineachcenter.

Ineachelectronicform,thefollowingsectionshadtothefilled: (1)Patient’sdata,includingdemographics,patient’ssource (outpa-tient,dayhospitalorhospitalized)andclinicalpriority(defined asurgentvs.electiveexam).

(2)Clinical indications to the exam, which were listed and readapted following the ACCF/ACR/SCCT/SCMR/ASNC/NASCI/ SCAI/SIRappropriatenesscriteriaforcardiaccomputed tomo-graphy and cardiac magnetic resonance imaging published

in 2006 and using the same organization proposed in the EuroCMRstudy,inordertoobtainreproducibleandcomparable data[7].

(3)Acquisitiondataconcerningmodel andfield strengthofthe scanner adopted,type and dose ofcontrast agents adopted andpresence/absence(andtypeofdrug)ofpharmacological stress.

(4)Adverse events occurring during or immediately after the examination, attributable to contrast agent administration and/or pharmacological stress and/or patient’s basal condi-tion. Complications caused by acute adverse reactions to contrastmedia(i.e.within60minafteradministration)were defined according to the American College of Radiology criteria[8].

Incidentswerescoredasmild,moderateorsevereusingthe followingpredefinedcriteriareadaptedfromDorfmanetal.[9]: (a)Mild: Transient change in condition, not life threaten-ingandrapidlyreturningtobaseline,requiredmonitoring and/or minor intervention such as holding a med-ication, obtaining lab test(s), application of heat or cold.

(b)Moderate:Transientchangeincondition,maybelife threat-ening if not treated, returning to baseline if properly treatedandrequiredmonitoringand/orinterventionsuch as reversal agent, additional medication, or transfer to ICU.

(c)Severe:Changeincondition,lifethreateningifnottreated andpotentiallypermanent,mayhaverequired hospitaliza-tionortransfertoICU,requiredmonitoringand/ormajor interventionsuchasinvasiveprocedure,intubation, hemo-dynamicsupportandbloodtransfusion.In caseofdeath, patientswereexcludedfromtheregistry,recordingcause oftheexitus.

(5)Imagequalityoftheexamwasalsoevaluatedona5-pointscale fromexcellenttoinadequateasfollows:

(1)insufficient:definedas“majorartifactsexistleadingto non-diagnosticimages”;

(2)‘poor’definedas“majorartifactspresentlimitingclinical useofimages”;

(3)‘fair’ defined as“borderline clinicaluseduetoadequate imagequality”;

(4)‘good’ defined as “only minor artifacts present with no/minimalimpactonclinicaluse”;

(5)‘excellent’definedas“noartifacts”.

(6)Resultoftheexamaccordingtothemainclinicalrequest(i.e. positive,negativeornon-diagnostic/inconclusive).

(7)Clinicalimpactonpatient’smanagement(meaningtherapeutic impactorrequiringfurthermanagement)whichwasassessed bythelocalreferralphysicianinconsensuswithpatient’s refer-ringphysicianandclassifiedasfollows:

(a)Nondiagnosticorinconclusiveexam.

(b)Relevantbutwithoutimpactonpatient’smanagement. (c)Relevantwithimpactonpatient’smanagement,consisting

inchangesinthetherapeutic(pharmacologicalorsurgical) ordiagnostic(furtherproceduresperformed)management and/or patient’s discardor hospitalization following the exam.

(8)Specialtyofthereadingandreportingphysician.

3. Dataextraction

Allthedatawerecollectedviaemail ona monthlybasis by trainedpersonnelandmanuallystoredinanelectronicdatabase providedbytheUniversity ofL’Aquilaforevaluation (Microsoft Excelversion2007).

Table1

Demographic,clinicalandacquisitiondata.

Studypopulation(n) 3376(100%) Geographicdistributionof

participatingcentersand%ofpatient’s enrolled

-21North(46.3%) -14Center(36.8%) -5SouthandIslands(16.9%) Gender Male:2254(67.0%);Female:1122

(33.0%) Meanage(years) 47.2±19.3(1–92) Bodymassindex(kg/m2_{) 24.8±2.2(21.6–27.4)}

Patient’ssource Outpatients:2070(61.0%) Dayhospital:232(7.0%) Hospitalized:1050(31.0%) Non-specified:23(1.0%) Clinicalpriority Urgent:6.5%;elective(91.6%) Scannertype(patient’senrolledand%) 1.0T:25(0.7%)

1.5T:3257(96.5%) 3.0T:92(2.8%)

4. Statisticalanalysis

Duetothedescriptivenatureofpresentregistry,allcollected

dataareexpressedintermsofabsolutenumbersand

correspond-ingpercentagesusingmeanswithstandarddeviation(SD)when

appropriate.Thisstudywasapprovedbylocalinstitutionalreview

boards.

5. Results

5.1. Patient’sdata

Databaseofpresentregistryincludes3376patientswhowere

prospectivelyenrolledduringthestudyperiod.

The average number of patients enrolled per center was

84.4±57.3SDwitharangebetween3and425.

Mean age(SD)was47.2±19 years, range 1–92years; 2254

(67.0%)patientsweremalesand1112(33.0%)werefemale.

Concerning geographic distribution of patient’s population,

therewasaclearnorth-to-southgradient,withthelargest

pro-portionofpatients(46.3%)enrolledfromthenorthofthecountry

(46.3%) followed by central regions (36.8%) whereas south and

islandscontributedfor16.9%ofoverallpopulation.

Detailedpatients’data,arereportedinTable1.

Clinical priority to theexam was defined urgent in 6.5% of patientsandelectivein91.6%ofcaseswhereasnoinformationwas availableintheremaining1.8%.

Urgentexamsweremostlyrequiredfortheevaluationofacute patients(myocarditisandacuteinfarctpatientsin70%ofcases)or followingasurgicalprocedure(21.0%).

Most of the examinations (2094 patients; 62.0%) were per-formedforoutpatients,232wereinadayhospital(7.0%)regimen and1050werehospitalized(31.0%).

5.2. Clinicalindicationstotheexam

Themajorityofexamswereperformedfortheworkupof inflam-matoryheartdisease/cardiomyopathiesrepresentingoverall55.7% ofcasesfollowedbytheassessmentofmyocardialviabilityand acuteinfarction(respectively6.9%and5.9%ofpatients).

Mostfrequentclinicalindicationsweresubstantiallybalanced withinthefirstgroupandincludedarrhythmogenicright ventri-cularcardiomyopathy(AVRC;11.2%)ironoverloadquantification (9.9%),acute myocarditis(9.8%),hypertrophicand dilatedCMPs (9.2%and8.7%respectively).

Table2

ClinicalindicationstoCMRwithcorrespondingexamination’sresults.

Clinicalindication Prevalence Negative Positive Non-diagnostic Nonspecified

ARVC 11.2% 72.0% 23.1% 2.6% 2.3% IronOverload 9.9% 14.7% 84.3% 0.7% 0.3% Acutemyocarditis 9.8% 31.1% 67.1% 0.9% 0.9% HCM 9.2% 21% 75.4% 2.0% 1.6% DCM 8.7% 16.0% 78.0% 3.0% 3.0% Viability 6.9% 17.7% 78.9% 0.7% 2.7% AMI 5.9% 14.0% 84.2% 0.9% 0.9% Ischemia/stress 3.0% 47.0% 49.0% – 4.0% Non-compaction 3.0% 45.7% 51.0% 1.1% 2.2%

Myocardialstoragedisease 2.2% 42.0% 56.0% 0.4% 1.6%

Cardiacandpericardialmasses 1.8% 20.3% 76.7% 2.0% 1.0%

Tako-tsubo 1.1% 17.0% 73.0% 2.0% 8.0% Congenitaldisease 0.6% 6.0% 93.0% 1.0% Valvulardisease 0.5% 3.0% 96.0% 1.0% Pericardialdisease 0.4% 19.0% 80.0% 1.0% Pulmonaryhypertension 0.4% 9.0% 90.0% 1.0% Biventricularfunction 0.3% 37.5% 62.5% – –

ARVC,arrhythmogenicrightventricularcardiomyopathy;HCM,hypertrophiccardiomyopathy;DCM,dilatedcardiomyopathy;AMI,acutemyocardialinfarction.

5.3. Acquisitiondata

Most of investigations were performed with 1.5T scanners

(96.5%),followedby3T(2.7%)and1Tsystems(0.8%)(Table2)and

contrastagentwasadministeredin84.8%oftheexams.

Apharmacologicstresstest,usingdipyridamole,adenosineor dobutamine,wasconductedon87cases(3.0%)(Table3).

Stressimagingmostlyconsistedinrest/stressperfusion stud-ies with adenosine or dipyridamole (overall 93.0% of exams) whereas dobutamine administration was used in only 7.0% of cases.

Listandaverageamountofcontrastagentsadministeredinboth restand stress CMRexaminations coupledwithpharmacologic stressprotocolsadoptedarereportedinTable3.

Acquisitiontimerangedbetween3and150minwithanaverage scanningdurationof43±13minperexam;differencesin aver-ageexaminationtimesignificantlyvariedbetweennon-contrast vs.restvs.stressexamsrangingbetween35,44and54min respec-tively(detaileddataarereportedinTable4)

5.4. Safetyevaluation

Safetyassessment revealed 30 (0.9%)adverse clinicalevents occurredduringorimmediatelyaftertheprocedure(i.e.<60min), mostofwhichwereattributedtopatient’spoorclinicalconditions priortotheexamination(n=20;66.6%oftheevents)(Fig.1).

Amongthisfirstgroupofpatients,eventswerescoredas mod-erateintwocasesduetotheoccurrenceofarrhythmiainacute infarctpatients,andmildintheremainingeighteenpatientsmostly

Fig.1. Barchartplottingtypeandseverityofadverseclinicaleventsoccurredduring orimmediatelyafter(i.e.<60min)CMRexamination.

consisting in dyspnea and claustrophobia almost exclusively observedinacuteinfarctpatients(n=17plus1patientwithHCM). Contrastmedia-relatedadverseeventswerereportedinonly sixcases(0.1%),andscoredasmildinfive(83.0%)andmoderate inone patientpresenting withvomit,facial swelling and bron-chospasmaftercontrastadministrationwhichrequiredshort-term observation.

In theremainingfourcases, adverseeffects occurredduring dipyridamolestressCMRandtwoweredirectlyrelatedtothedrug administrationwithanginawhereasclaustrophobiawasreferred intheremainingtwo.

Noseverereactionsorcasesofdeathwerereportedduringor becauseoftheCMRprocedure.

5.5. Resultoftheexam,imagequalityandimpactonpatient’s management

Imagequalitywasscoredfromexcellenttogoodin82%ofcases (fair:7.1%;poor:6.3%;insufficient:2.2%)andnoinformationwere availablein96patients(2.0%).

In 65.0% of cases, CMRwaspositive and thefinal diagnosis obtainedwasconsideredclinicallyrelevantin85.4%ofthecases providingsignificantimpactonclinical/therapeuticmanagement in49.4%ofpatients.Overall,only6.0%ofthediagnoseshadno clin-icalrelevanceandapproximately1%ofexamswerenotdiagnostic (Fig.2).

Thehighestprevalenceofnegativeexaminationswasobserved inpatientswithsuspectedARVD(72.0%),followedbythosewith non-compactedmyocardium(45.4%).

The highest impact on patient’s management was reported in stress examinations for CAD (68.0% of the cases), followed bytheassessmentandquantification ofironoverload(64.0%of cases),suspectedacutemyocarditis(60%ofcases),anddilated car-diomiopathy(54.0%),whereasin61.1%and52.3%ofpatientswith respectivelyTako-tsuboCMPandacutemyocardialinfarctionthe examinationwasfoundtohavenoimpactonclinicalanddiagnostic workup.

6. Reportingphysicians

Overall80.1%oftheexamswerereportedbyradiologistsalone (12.9% with double specialization in radiology/cardiology) and 17.0% by radiologists and cardiologists in consensus whereas, in our series,cardiologists alone represented 2.6% of reporting physicians.

Table3

Contrastadministrationprotocolsinrestandstressexams.

Gadoliniumchelate Patients(n) Min.dose(mmol/kg) Max.dose(mmol/kg) Averagedose(mmol/kg) Stress

Gadotericacid 170 0.1 0.2 0.18 3 Gadopentetatedimeglumine 619 0.1 0.2 0.16 35 Gadobenatedimeglumine 776 0.05 0.25 0.16 41 Gadobutrol 1257 0.05 0.3 0.22 8 Gadodiamide 4 0.1 0.2 0.17 0 Gadoteridol 5 0.2 0.2 0.2 0

Gadoversetamide 11 Nonspec Nonspec Nonspec 0

Non-specified 534 – – –

Table4

CMRprotocolsandacquisitiontime.

CMRProtocol N % Minimal acquisitiontime Maximal acquisitiontime Average NostressnoGadolinium 726 22.0 3 ₇₀ ₃₅ Nostress+gadolinium 2420 75.0 6 150 44 Stress+nogadolinium 7 .02 20 60 43 Stress+gadolinium 91 0.3 25 ₉₀ ₅₄ Total 3244 – 16 ₉₄ ₄₄ 7. Discussion

This Italian CMR survey was designed to evaluate

dif-fusion and geographic distribution of the various national

centers performing the exam, verifying technical equipment,

protocolsadopted, safety profile and spectraof clinical

indica-tions.

Besidesproviding“locally”usefuldatahowever,thisregistry

representsalargepatient’sdatabaserecruitedinarelativelyshort

timeinterval(3376patientsduringasix-monthperiodof

enroll-ment)andderivedfromtheexperiencesoffortydifferentcenters,

usingmultivendor equipmentand contrastagentsand covering

variablelevelsofCMRexpertiseduetotheopen-accessnatureof

thestudy.

Afurtherelementofevaluationisthepredominant

radiolog-icalinvolvementofparticipatingsitescharacterizedby80.1%of

examsreadandreportedbyradiologists(including12.9%ofdouble

specialtyphysicians)plus17.0%ofcasesperformedinconsensus

withcardiologistswithrelevant differencesfromtheEuro-CMR

datainwhichroleofradiologistswaslimitedtoonly2.6%ofcases

withan additional 26.7% ofcases read by a combinedteam of

cardiologistandradiologists[3].Thisdiscrepancycanbeattributed

to a “specialty-oriented” bias in the selection of referring cen-tersrelatedtothedifferentbackgroundofgroupswhoinitiated andpromotedbothregistriesrepresentingrespectivelytheCMR working group of the European Society of Cardiology and the Working Group of the Cardiac Radiology Section of the SIRM. Radiologically “imbalanced” data were also published in 2006 by Levin and coll. who reported a 91% prevalence of exams performed by radiologist in a large Medicare-based patient’s database of 110,743 CMR studies analyzed [1]. An additional general bias of any registry like ours regards the intrinsic impossibility todeterminetheexact degreeofcompletenessof patient’senrollmentpercenterwithobviouspotentialand unpre-dictable impact onprevalence of indications and on resultsin general.

7.1. Technicalequipmentandacquisitionprotocols

StateoftheartofCMRimagingisperformedinItalyusing1.5T magnetsinthevastmajorityofcases(96.5%ofexams)whereasuse of3Tscannerswaslimitedinourdatabaseto2.7%ofpatients.

Theseresultsaresubstantiallyinlinewiththoseofthe Euro-CMR(0.5%ofstudiesperformedwith3Tmachines)andconfirm thatboththehigherscanners’costsandtechnicalchallenges(field homogeneityreductionwithincreasedsusceptibilityartifactsand radiofrequency-inducedpowerdeposition)associated withhigh fieldsystemsarestillperceivedasmajordrawbacksbymost cen-terslimitingtheirdiffusionandutilizationintheterritoryonlyto fewresearchsitesregardlesssignificantrecentimprovementsand potentialadvantagesof3TimaginginCMR[5,10,11].

Mostof theexaminationswereperformed withintravenous administrationofcontrastagents(84.8%),confirmingthatCMRis acontrast-dependenttechniqueinmostofthecasesanditsability intissuecharacterizationisfurtherenhancedbyuseofgadolinium andlateenhancementtechniquesallowingtocharacterize myocar-dialdiseasewithdifferentlateenhancementpatternsinalarge varietyofclinicalconditions[12–15].

Pharmacological stress was performed in only 3.0% of our patients’populationascomparedtotheEuro-CMRregistryinwhich perfusionand/orfunctionalstressprotocolswereusedin34.2%of casestoruleoutmyocardialischemiaandviability[5].Stress imag-ingmostlyconsistedinrest/stressperfusionstudieswithadenosine or dipyridamole (overall93.0% of exams)whereas dobutamine administrationwasusedfortheassessmentofinducibleischemia inonly7.0%ofcaseslikelyasaconsequenceofthelowersafety pro-fileofthedrugathigherdoses,withmajoreventsreportedin3–21% ofpatientsandrequiringresuscitationMR-compatibleequipment andmedicationsmanagedbydedicatedmedicalstaff[16].Thelow prevalenceofstressexamsinourpatient’spopulationhighlightsan importantfeatureofpresentregistry,whichmainlyreports activ-ity,performedinradiologicalunitsascomparedtotheprominent clinical/cardiologicalbackgroundoftheEuroCMR.Thisobservation accountsthedifferentattitudeofcardiologiststowarduseofstress imagingfortheevaluationofCADandaprobablydeeperclinical comprehensionoftheaddedvalueofMRinthisclinicalsettingas comparedtoechocardiographyorSPECT[17].Anadditionalissue toconsiderinthisregard,concernstheextremelyvariable experi-enceofthecentersinvolvedwhichmighthaveorientedadifferent pathologyfocusinlessspecializedsitesinfavorofmore manage-ableandeasilyapproachableindications(seeSection7.2).

Thedirectiontofollowisalsolikelytofurthereducatereferral physiciansregardingCMRaddedclinicalvalueintheclinicalsetting ofmyocardialischemia.

7.2. Clinicalindicationsandimpactonpatient’smanagement Themajorityofexamswereperformedfor theevaluation of inflammatoryheartdisease/cardiomyopathies,representing over-all55.7%ofcasesascomparedtotherespectively6.9%and5.9%of patientsaddressedformyocardialviabilityassessmentandacute myocardialinfarction(Table2).

These indications again show a remarkable difference from the recently updated results of the Euro-CMR registry, in which ischemia and suspected CAD surpassed myocardi-tis/cardiomyopathies (respectively 34.2% vs. 32.2%) with an additional 14.6% of patients examined for myocardial viability assessment[5].

Ratherthanasinglepredominantclinicalrequest,therewere fivesubstantiallybalancedmostfrequentindicationsinourseries, rangingbetween11.2%and8.7%ofcasesandrepresented(inorder) byARVC,ironoverloadquantification,acutemyocarditis, hyper-trophicanddilatedCMPs.

Aorticdiseasewasnotincludedinthelistofourexamsaswe meanttospecificallyfocusoncardiacpathologyreferringtogreat vesselsonlyinpresenceofpredominantmyocardialinvolvement (likeincongenitalheartdiseaseandpulmonaryhypertension).

Interestingly,listofindicationsreportedinTable2accountsfor only74.9%ofalltheexamsrecordedinourregistryandhighlights thattherewasasignificant25.1%ofstudieswhichwereclassified as“othersindications”or“non-specifiedclinicalrequest”.

Thereasonforthisresultmightbeeitherattributabletothelack ofclinicalinformationatthemomentofCMRexaminationormore likelysimplyreflectsahighrateofincompletefillingofpatient’s electronicformsbyreferringcenters.

ARVCwasthefirstindicationofourregistry(11.2%ofexams), whichispartiallyexplainablewiththerelativelyhighprevalence of this disease in the Italian territory [18,19] and most likely dependsontheuniquediagnosticcontributionofferedbyCMRin thiscardiomyopathyallowingtoidentifythevarious morphologi-calandfunctionalhallmarksofthedisease[20–22].Despitethelow incidenceofdisease,wehadanunexpectedprevalenceof23.0% positivecasesinourpatient’spopulationrepresentinganunlikely falsepositiveratelikelyattributabletothetrendtoover-reading andover-diagnoseARVDinlessexperiencedoperatorswhichwas previouslydescribedbySen-Chowdhryetal.[23];thistrendmay becausedbythedifficultyinrecognizinganddiscriminating nor-malvs.abnormalmorphologicalandfunctionalfindingswithinthe thin-walled,trabeculated,complexanatomyoftherightventricle. SecondCMRindicationofourdatabase(9.9%)wastheevaluation ofpatientswithprimaryorsecondaryformsofmyocardial sidero-sisinwhichuseofmultiechogradientechoT2*sequencesallows todiagnoseandquantifymyocardialironoverloadinapreclinical stageandtomonitoreffectsofchelationtherapyofferingimportant insightsforunderstandingthepathophysiologyofiron accumula-tionandthecomplexdynamicsofitspharmacologicalclearance

[24,25].

Thehighprevalenceofthisrequestinourpatient’scohortalso probablydependsontheepidemiologyof␤-thalassemiainItaly, whichisendemicinspecificareasofthecountryincludingmajor islands(SicilyandSardinia),thelowerPovalleyandtheregions ofLazio,PugliaandCalabria[26].Impactoftheexaminthis clini-calsettingwasregardedamongthehighestofourpatient’scohort (onlyfollowingtherelativelylimitednumberofstress-exams per-formed)withasignificantinfluenceonpatient’smanagementin 64.0%of thecaseswhich indirectlyconfirms theimportanceto routinely(atleastonanannualbase)evaluatecardiacT2*ofall chronicallytransfusedpatients[27].

Afurthercommonandhigh-impactindicationwasthe evalua-tionofpatientswithsuspectedacutemyocarditis(9.8%ofexams), inwhichCMRaddressedadifferenttherapeutic/diagnostic/clinical managementin60%ofcasesinrecognitionofthehighsensitivity oftheexamtodetectsignsofactiveinflammationrepresentedby edema,capillaryleakageandfibrosis/necrosis[16].

DiagnosticworkupofdilatedandhypertrophicCMPswasalso frequentlyrequiredinourseries(respectively9.2%and8.7%)with animportantcontributionacknowledgedtotheexam(relevantand withimpactonmanagementinrespectively54%and41%ofcases) reflectingitsroleinthedifferentialdiagnosisbetweenthevarious typesofdilatedand hypertrophicphenotypesofdiseaseandits importantprognosticimplications[28–30].

7.3. Safetyprofile

Ourpatient’scohortdataconfirmthehighsafetyprofileofCMR examinationwithoverallonly30(0.9%)adversemildormoderate clinicaleventsrecordedduringorimmediatelyaftertheprocedure withoutoccurrenceofseverereactions/death.

Mostoftheeventswereobservedinpatientswithacute myocar-dialinfarction (17cases)andwere relatedtopatient’s baseline clinicalconditionswithonsetofarrhythmiasand/ordyspnea dur-ingCMRrequiringtoendtheexamination.

Contrastmediarelated adverseeffectswerereportedinonly 0.18%(n=6)ofadministrationsmostlyconsistinginmildreactions (n=5) withonly onepatient presentinga moderate anaphylac-toidreactionrequiring short-termmonitoringbeforedischarge. Ourresultsarecompletelyinlinewiththerecentlypublisheddata extracted fromtheEuro-CMRstudy inwhich 30 acute adverse reactions (0.17%) occurred in a large cohort of 17,767 doses administered[31].Similarfindingswerereportedinlargerstudies analyzingtheincidenceofgadolinium-relatedcontrastmedia reac-tionsreportingeventratesrangingbetween0.04and2.2%[32–34]. Wecouldnotanalyzedifferencesinreactionratesbetweenthe variousgadolinium-basedcontrastmoleculesduetothelimited numberof eventsobservedinourpopulationalthougha lower adversereactionsincidencefornonionicgadolinium-based con-trastagentshasbeenreportedinliteratureascomparedtoionic linearormacrocyclicagents[32].

Ourstudydesigndidalsonotincludepatient’sfollow-upafter contrastadministration,thusexcludingthepossibilitytoidentify latecontrast-relatedadversereactionssuchasnephrogenic sys-temicfibrosis(NSF),whichhasbeenhowevervirtuallyeliminated bypreventivemeasuresincludingscreening forthepresenceof renaldysfunctioninallpatientsrequiringgadolinium-enhanced MRevaluation.

Adverseeventsrelatedtopharmacological-stresswerereported infourcasesandattributedtodrug’scollateraleffectsonlyintwo patientsundergoingdypiridamolestressmyocardialperfusionand scoredasmild(angorinbothcases).Thelimitednumberofstress examsperformedinourregistrylimitsanysafetyprofile evalua-tionalthoughbothperfusionandfunctionalstressCMRhavebeen reportedtobesafe,accurateandwithminimalsideeffectsin sev-eralstudiesandliteraturemetanalysis[16,35].

8. Conclusions

OurregistryhasshownawidediffusionofcardiacMR-dedicated centersinItalywhicharemostlyconduictedbyradiologist.

Relevantdifferenceshaveemergedintermsofclinical indica-tionsbetweentheSIRMand Euro-CMRdatabasesasa resultof thedifferentclinicalandculturalbackgroundsofthegroupsand sitesinvolved,butalsoreflectingdifferentdiseasesepidemiology, witha prevalenceofexamsaddressedforiron-overload assess-mentandsuspectedARVDandalimitednumberofstress-studies performedinourpatient’scohort.Inmostcases,diagnostic con-tributionprovidedbytheexaminationwasregardedassignficant andwithimpactonclinicalmanagement.

Thelimitedincidenceandlowseverityofadverseclinicalevents observedinourregistryconfirmsthatCMRisasafeexamination withalowrateofacutecontrast-relatedadversereactionswhich wassimilarinourpatient’sdatabasetoliteraturedata.

FurtherresearchfocusofCMRregistrieswouldprobablyrequire systematicclinicalfollow-upofpatient’senrolledinorderto ana-lyzemid-andlong-termimplicationsofCMRfindingsproviding widercomprehensionofitsclinicalroleinthecomplexscenarioof cardiovasculardiseases.

References

[1]LevinDC,RaoVM,FrangosAJ,ParkerL,SunshineJH.Thecontroversyover advancedcardiovascularimaging:relativerolesofradiologists,cardiologists, andotherphysiciansinCTandMRIofthecardiovascularsystem.Journalofthe AmericanCollegeofRadiology:JACR2006;3(1):16–8.

[2]DiCesareE,CademartiriF,CarboneI,etal.Clinicalindicationsfortheuse ofcardiacMRI.BytheSIRMstudygrouponcardiacimaging.RadiolMed 2013;118(5):752–98.

[3]BruderO,SchneiderS,NothnagelD,etal.EuroCMR(Europeancardiovascular magneticresonance)registry:resultsoftheGermanpilotphase.Journalofthe AmericanCollegeofCardiology2009;54(15):1457–66.

[4]Bruder O, Wagner A,Mahrholdt H. Lessons learned from the European cardiovascularmagneticresonance(EuroCMR)registrypilotphase.Current CardiovascularImagingReports2010;3(3):171–4.

[5]BruderO,WagnerA,LombardiM,etal.Europeancardiovascularmagnetic resonance(EuroCMR)registry–multinationalresultsfrom57centersin15 countries.JournalofCardiovascularMagneticResonance:OfficialJournalofthe SocietyforCardiovascularMagneticResonance2013;15:9.

[6]ThomasB,TavaresNJ.DotheresultsoftheGermanpilotphaseoftheEuroCMR Registryindicatethatthechasmhasbeencrossed?JournaloftheAmerican CollegeofCardiology2010;55(4):412.

[7]HendelRC,PatelMR,KramerCM,etal.ACCF/ACR/SCCT/SCMR/ASNC/NASCI/ SCAI/SIR2006appropriatenesscriteriaforcardiaccomputedtomographyand cardiacmagneticresonanceimaging:areportoftheAmericanCollegeof Car-diologyFoundationQualityStrategicDirectionsCommitteeAppropriateness CriteriaWorkingGroup,AmericanCollegeofRadiology,Societyof Cardiovas-cularComputedTomography,SocietyforCardiovascularMagneticResonance, AmericanSocietyofNuclearCardiology,NorthAmericanSocietyforCardiac Imaging,SocietyforCardiovascularAngiographyandInterventions,and Soci-etyofInterventionalRadiology.JournaloftheAmericanCollegeofCardiology 2006;48(7):1475–97.

[8]American College of Radiology. Manual on contrast media: version 9 —2013 [book online].Reston, VA:American College of Radiology.2013.

http://www.acr.org/∼/media/ACR/Documents/PDF/QualitySafety/Resources/ Contrast%20Manual/13ContrastMedia.pdf

[9]DorfmanAL,OdegardKC,PowellAJ,LaussenPC,GevaT.Riskfactorsforadverse eventsduringcardiovascularmagneticresonanceincongenitalheartdisease. JournalofCardiovascularMagneticResonance:OfficialJournaloftheSociety forCardiovascularMagneticResonance2007;9(5):793–8.

[10]OshinskiJN,DelfinoJG,SharmaP,GharibAM,PettigrewRI.Cardiovascular magneticresonanceat3.0T:currentstateoftheart.JournalofCardiovascular MagneticResonance:OfficialJournaloftheSocietyforCardiovascularMagnetic Resonance2010;12:55.

[11]HaysAG,ScharM,KelleS.Clinicalapplicationsforcardiovascularmagnetic resonanceimagingat3tesla.CurrentCardiologyReviews2009;5(3):237–42.

[12]VermesE,CarboneI,FriedrichMG,MerchantN.Patternsofmyocardiallate enhancement:typicalandatypicalfeatures.ArchivesofCardiovascular Dis-eases2012;105(5):300–8.

[13]HunoldP,SchlosserT,VogtFM,etal.Myocardiallateenhancementin contrast-enhancedcardiacMRI:distinctionbetweeninfarctionscarand non-infarction-relateddisease.AmericanJournalofRoentgenology2005;184(5):1420–6.

[14]OrdovasKG,HigginsCB.DelayedcontrastenhancementonMRimagesof myocardium:past,present,future.Radiology2011;261(2):358–74.

[15]Masci PG, Francone M, Desmet W, et al. Right ventricular ischemic injury in patients with acute ST-segment elevation myocardial infarc-tion:characterization withcardiovascularmagneticresonance.Circulation 2010;122(14):1405–12.

[16]AmericanCollegeofCardiologyFoundationTaskForceonExpertConsensus D,HundleyWG,BluemkeDA,etal.ACCF/ACR/AHA/NASCI/SCMR2010expert consensusdocumentoncardiovascularmagneticresonance:areportofthe AmericanCollegeofCardiologyFoundationTaskForceonExpertConsensus Documents.JAmCollCardiol2010;55(23):2614-62.

[17]SchwitterJ,WackerCM,vanRossumAC,etal.MR-IMPACT:comparisonof perfusion-cardiacmagneticresonancewithsingle-photonemissioncomputed tomographyforthedetectionofcoronaryarterydiseaseinamulticentre, mul-tivendor,randomizedtrial.EuropeanHeartJournal2008;29(4):480–9.

[18]NavaA,ThieneG,CancianiB,etal.Familialoccurrenceofrightventricular dysplasia:astudyinvolvingninefamilies.JournaloftheAmericanCollegeof Cardiology1988;12(5):1222–8.

[19]ThieneG,CorradoD,BassoC.Arrhythmogenicrightventricular cardiomyopa-thy/dysplasia.OrphanetJournalofRareDiseases2007;2:45.

[20]JainA,TandriH,CalkinsH,BluemkeDA.Roleofcardiovascularmagnetic resonanceimaginginarrhythmogenicrightventriculardysplasia.Journalof CardiovascularMagneticResonance:OfficialJournaloftheSocietyfor Cardio-vascularMagneticResonance2008;10:32.

[21]CastilloE,TandriH,RodriguezER,etal.Arrhythmogenicrightventricular dys-plasia:exvivoandinvivofatdetectionwithblack-bloodMRimaging.Radiology 2004;232(1):38–48.

[22]MarcusFI,McKennaWJ,SherrillD,etal.Diagnosisofarrhythmogenicright ventricularcardiomyopathy/dysplasia:proposedmodificationofthetaskforce criteria.EuropeanHeartJournal2010;31(7):806–14.

[23]Sen-ChowdhryS,PrasadSK,SyrrisP,etal.Cardiovascularmagneticresonance inarrhythmogenicrightventricularcardiomyopathyrevisited:comparison withtaskforcecriteriaandgenotype.JournaloftheAmericanCollegeof Car-diology2006;48(10):2132–40.

[24]AndersonLJ,HoldenS,DavisB,etal.CardiovascularT2-star(T2*)magnetic resonancefortheearlydiagnosisofmyocardialironoverload.EuropeanHeart Journal2001;22(23):2171–9.

[25]OoiGC,KhongPL,ChanGC,etal.Magneticresonancescreeningofironstatusin transfusion-dependentbeta-thalassaemiapatients.BritishJournalof Haema-tology2004;124(3):385–90.

[26]Silvestroni E, Bianco I. Screening for microcytemia in Italy: analysis of datacollectedinthepast30years.AmericanJournalofHumanGenetics 1975;27(2):198–212.

[27]WoodJC.ImpactofironassessmentbyMRI,Hematology/theeducation pro-gramoftheAmericansocietyofhematology.AmericanSocietyofHematology EducationProgram2011;2011:443–50.

[28]ElliottP, Andersson B, ArbustiniE,et al. Classification ofthe cardiomy-opathies: a position statement from theEuropean society of cardiology workinggrouponmyocardialandpericardialdiseases.EuropeanHeartJournal 2008;29(2):270–6.

[29]RapezziC,ArbustiniE,CaforioAL,etal.Diagnosticwork-upin cardiomy-opathies:bridgingthegapbetweenclinicalphenotypesandfinaldiagnosis.A positionstatementfromtheESCworkinggrouponmyocardialandpericardial diseases.EuropeanHeartJournal2012.

[30]Flett AS,Westwood MA, Davies LC, Mathur A, MoonJC. Theprognostic implicationsofcardiovascularmagneticresonance.CirculationCardiovascular Imaging2009;2(3):243–50.

[31]Bruder O, Schneider S, Nothnagel D, et al. Acute adverse reactions to gadolinium-based contrast agents in CMR: multicenter experience with 17,767 patientsfrom theEuroCMRregistry.JACCCardiovascularImaging 2011;4(11):1171–6.

[32]PrinceMR,ZhangH,ZouZ, StaronRB, BrillPW.Incidence ofimmediate gadoliniumcontrastmediareactions.AJRAmericanJournalofRoentgenology 2011;196(2):W138–43.

[33]HuntCH,HartmanRP,HesleyGK.Frequencyandseverityofadverseeffectsof iodinatedandgadoliniumcontrastmaterials:retrospectivereviewof456,930 doses.AJRAmericanJournalofRoentgenology2009;193(4):1124–7.

[34]AbujudehHH,KosarajuVK,KaewlaiR.Acuteadversereactionsto gadopen-tetatedimeglumineandgadobenatedimeglumine:experiencewith32,659 injections.AJRAmericanJournalofRoentgenology2010;194(2):430–4.

[35]Wahl A,Paetsch I, Gollesch A, etal. Safety and feasibility ofhigh-dose dobutamine-atropinestresscardiovascularmagneticresonancefordiagnosis ofmyocardialischaemia:experiencein1000consecutivecases.EuropeanHeart Journal2004;25(14):1230–6.