和心肌病基因检测情况欧洲专家共识

HRS/EHRAExpertConsensusStatementontheStateofGeneticTestingfortheChannelopathiesandCardiomyopathiesThisdocumentwasdevelopedasapartnershipbetweentheHeartRhythmSociety(HRS)andtheEuropeanHeartRhythmAssociation(EHRA)MichaelJ.Ackerman,MD,PhD,1SilviaG.Priori,MD,PhD,2StephanWillems,MD,PhD,3CharlesBerul,MD,FHRS,CCDS,4RamonBrugada,MD,PhD,5HughCalkins,MD,FHRS,CCDS,6A.JohnCamm,MD,FHRS,7PatrickT.Ellinor,MD,PhD,8MichaelGollob,MD,9RobertHamilton,MD,CCDS,10RayE.Hershberger,MD,11DanielP.Judge,MD,6,12HervèLeMarec,MD,13WilliamJ.McKenna,MD,14EricSchulze-Bahr,MD,PhD,15ChrisSemsarian,MBBS,PhD,16JeffreyA.Towbin,MD,17HughWatkins,MD,PhD,18ArthurWilde,MD,PhD,19ChristianWolpert,MD,20DouglasP.Zipes,MD,FHRS211FromMayoClinic,Rochester,Minnesota,2FondazioneSalvatoreMaugeriUniversityofPavia,Pavia,ItalyandNewYorkUniversity,NewYork,NewYork,3UniversityHospitalHamburg-Eppendorf,Hamburg,Germany,4Children’sNationalMedicalCenterandGeorgeWashingtonSchoolofMedicine,Washington,DistrictofColumbia,5GironaInstituteofBiomedicalResearchandUniversityofGironaSchoolofMedicine,Girona,Spain,6JohnsHopkinsUniversity,Baltimore,Maryland,7St.George’sUniversityofLondon,London,UnitedKingdom,8MassachusettsGeneralHospital,CardiacArrhythmiaService,Boston,Massachusetts,9UniversityofOttawaHeartInstitute,Ottawa,Canada,10HospitalforSickChildren,Toronto,Canada,11UniversityofMiamiMillerSchoolofMedicine,Miami,Florida,12UniversitéParisDescartes,Paris,France,13l’Institutduthorax,NantesCedex,Nantes,France,14InstituteofCardiovascularScience,UniversityCollegeLondon,London,UnitedKingdom,15UniversityHospitalMuenster,Muenster,Germany,16UniversityofSydney,Sydney,Australia,17CincinnatiChildren’sHospital,Cincinnati,Ohio,18UniversityofOxford,JohnRadcliffeHospital,Oxford,UnitedKingdom,19UniversityofAmsterdam,AcademicMedicalCenter,Amsterdam,TheNetherlands,20LudwigsburgClinic,Ludwigsburg,Germany,and21KrannertInstituteofCardiology,IndianaUniversitySchoolofMedicine,Indianapolis,Indiana.PreambleThisinternationalconsensusstatementprovidesthestateofgenetictestingforthechannelopathiesandcardiomy-opathies.Itsummarizestheopinionoftheinternationalwritinggroupmembersbasedontheirownexperienceandonageneralreviewoftheliteraturewithrespecttotheuseandroleofgenetictestingforthesepotentiallyheritablecardiacconditions.Thisdocumentfocusespri-marilyonthestateofgenetictestingforthe13distinctentitiesdetailedandtherelativediagnostic,prognostic,andtherapeuticimpactofthegenetictestresultforeachentity.Itdoesnotfocusonthetherapeuticmanagementofthevariouschannelopathiesandcardiomyopathies.Treatment/managementissuesareonlydiscussedforthosediseases(i.e.,LQTS,HCM,DCM
CCD,RCM)inwhichthegenetictestresultcouldpotentiallyinfluencetreatmentconsiderations.Writingrecommendationsforgeneticdiseasesrequireadaptationofthemethodologynormallyadoptedtoprepareguidelinesforclinicalpractice.Documentsproducedbyotherscientificsocietieshaveacknowledgedtheneedtodefinethecriteriausedtorankthestrengthofrecommen-dationforgeneticdiseases.1Themostobviousdifferenceisthatrandomizedand/orblindedstudiesdonotexist.Instead,mostoftheavail-abledataarederivedfromregistriesthathavefollowedpatientsandrecordedoutcomeinformation.TheauthorsofthisstatementhavethereforedefinedspecificcriteriaforClassI,ClassIIaorb,andClassIIIrecommendationsandhaveusedtheconventionallanguageadoptedbyAHA/ACC/ESCGuidelinestoexpresseachclass.Allrecommendationsarelevelofevidence(LOE)C(i.e.,basedonexperts’opinions).AClassIrecommendation(“isrecommended”)wasappliedforgenetictestinginindexcaseswithasoundclinicalsuspicionforthepresenceofachannelopathyoracardiomyopathywhenthepositivepredictivevalueofagenetictestishigh(likelihoodofpositiveresult40%andKEYWORDSGenetics;Cardiomyopathies;Channelopathies(HeartRhythm2011;8:1308–1339)TheHeartRhythmSocietyandEuropeanHeartRhythmAssociationendorsedthedocumentinAprilof2011.TheAmericanHeartAssociationendorsedthedocumentinJuneof2011.Correspondenceandreprintrequests:SonjaOlson,HeartRhythmSociety,1400KStreetNW,Wash-ington,DC20005.E-mailaddress:[e-mail].1547-5271/$-seefrontmatter©2011HeartRhythmSocietyandEuropeanHeartRhythmAssociation,aregisteredbranchoftheEuropeanSocietyofCardiology.PublishedbyElsevierInc.Allrightsreserved.doi:10.1016/j.hrthm.2011.05.020signal/noiseratio10;Table3),AND/ORwhenthegenetictestresultprovideseitherdiagnosticorprognosticinforma-tion,orwhenthegenetictestresultinfluencestherapeuticchoicesaccordingtodatainFigure1andinTable3.Inalltheremainingsituations,theauthorshaveusedeither“canbeuseful”toarticulateeitheraClassIIarecommendationor“maybeconsidered”tosignifyaClassIIbrecommendation.AClassIII(“shouldnot”or“isnotrecommended”)recom-mendationwasappliedincasesinwhichitwasagreedthatthegenetictestresultfailedtoprovideanyadditionalbenefitorcouldbeharmfulinthediagnosticevaluationofpatientswithpossibleinheritedheartdisease.Screeningoffamilymembersforthemutationidenti-fiedintheprobandofthefamilyisrecommendedasaClassIwhengenetictestingleadstotheadoptionoftherapy/protectivemeasures/lifestyleadaptations.Con-versely,theauthorshaveassignedaClass