NT-proBNP中国专家共识汇总

NT-proBNP中国专家共识汇总 NT-proBNP在急性心力衰竭中的应用 NT-proBNP在慢性心力衰竭中的应用 NT-proBNP的影响因素及其参考值Inthisstudy,followingenrollment,extensiveclinicaldatawerecollected,includingresultsofdiagnosticstudies.Inordertoascertainclinicalaccuracyforthediagnosisofheartfailure,themanagingEDphysicianwasasked—followingcompletionofevaluation—fortheirestimateofthepresenceofheartfailure.NT-proBNP在急性心力衰竭中的应用 NT-proBNP在急性心力衰竭诊断中的应用 NT-proBNP在急性心力衰竭预后评估中的应用 NT-proBNP在急性心力衰竭治疗监测中的应用Inthisstudy,followingenrollment,extensiveclinicaldatawerecollected,includingresultsofdiagnosticstudies.Inordertoascertainclinicalaccuracyforthediagnosisofheartfailure,themanagingEDphysicianwasasked—followingcompletionofevaluation—fortheirestimateofthepresenceofheartfailure.NT-proBNP检测用于有急性症状患者的心力衰竭诊断和排除国外评价NT-proBNP在急性呼吸困难中鉴别心衰的研究 新西兰Christchurch研究（2003年，205例） 西班牙Barcelona研究（2004年，100例） PRIDE研究（2005年，599例） ICON研究（2006年，1256例）Januzzietal,AmJCardiol2005;95:948Inthisstudy,followingenrollment,extensiveclinicaldatawerecollected,includingresultsofdiagnosticstudies.Inordertoascertainclinicalaccuracyforthediagnosisofheartfailure,themanagingEDphysicianwasasked—followingcompletionofevaluation—fortheirestimateofthepresenceofheartfailure.PRIDE研究Januzzietal,AmJCardiol2005;95:948前瞻性，盲性，针对599位到麻省总医院急症室主诉呼吸困难患者的研究ThemostdefinitivedatasupportingNT-proBNPusecamefromtheProBNPInvestigationofDyspneaintheEmergencyDepartment(PRIDE)Study.Inthisanalysisof599subjectswithdyspnea,NT-proBNPwastestedwiththehypothesisthatitwouldbeusefultobothdiagnoseandexcludeheartfailure.急性呼吸困难中HF的最佳独立预测因素Januzzietal,AmJCardiol2005;95:948 预测因素 OR 95%CI P值 NT-proBNP升高 44.0 21.0-91.0 <.001 胸片间质水肿 11.0 4.5-26.0 <.001 端坐呼吸 9.6 4.0-23.0 <.001 袢利尿剂的应用 3.4 1.8-6.4 .01 体检有啰音 2.4 1.2-5.2 .05 年龄(每年) 1.03 1.01-1.05 .01 咳嗽 .43 .23-.83 .05 发热 .17 .05-.50 .03InthePRIDEstudy,severalindependentpredictorsofadiagnosisofheartfailureinacutedyspneawereidentified:theseincludedfactorsfromhistoryandphysicalexamination,aswellasadjunctivetestingsuchaschestradiographyandNT-proBNPtesting.Asdemonstrated,NT-proBNPresultswerepowerfully,independentlypredictiveofadiagnosisofheartfailure.NT-proBNP诊断心衰准确性优于临床判断NT-proBNPversusClinicalJudgment,P=.006CombinedversusNT-proBNP,P=.04CombinedversusClinicalJudgment,P<.001AsPRIDEwasperformedtoevaluatetheimportanceofNT-proBNPresultsrelativetoclinicaljudgment,thesevariableswereputintoanROCanalysis.ClinicaljudgmenthadexcellentareaundertheROCof0.90;NT-proBNPalonehadanareaundertheROCof0.94,whichwassignificantlybetterthanclinicaljudgmentalone,howeverthecombinationofNT-proBNPPLUSclinicaljudgmentwassuperiortoeitheralone.Thissendsthereassuringmessagethatbiomarkertestingtogetherwithclinicaljudgmentisthesuperiorapproachtoevaluationofacutedyspnea.截定点900pg/mL能为在呼吸困难患者中诊断急性心力衰竭提供极好的准确性Januzzietal,AmJCardiol2005;95:948 独立于年龄WhenconsideringNT-proBNPresultsasafunctionofafinaldiagnosisofheartfailure,weseethatasinglecut-pointof900pg/mLprovidesoutstandingsensitivityandspecificityforthediagnosisofheartfailure,withresultsextraordinarilycomparabletoBNPof100pg/mL.However,similartoBNPof100pg/mL,NT-proBNPat900pg/mLhadapositivepredictivevalueof76%,whichimpliesthatfactorsbesidesacuteheartfailuremayresultinelevationsofbothmarkersintheabsenceofthediagnosis.NT-proBNP的国际合作Januzzietal,EurHJour2006;27:3301256位个体,720有急性心力衰竭ThiswastheprimarygenesisoftheInternationalCollaborativeofNT-proBNP(orICON)study.Inthispooledanalysisof1256patients(720ofwhomhadacuteheartfailure)fromBoston,Barcelona,Maastricht,andChristchurch,thevalueofNT-proBNPfordiagnosticandprognosticevaluationofheartfailurewasexplored.使用年龄分层的NT-proBNP“纳入”截定点可提高心衰诊断的准确性 NT-proBNP最佳的心衰排除截定点是300ng/ml NT-proBNP诊断急性心力衰竭时须进行年龄分层Januzzietal,EurHJour2006;27:330Incontrasttoanage-independentruleoutcut-point,theICONinvestigatorsfoundthatagestratificationofthe‘rulein’cut-pointforNT-proBNPyieldedsuperioraccuracycomparedtoasingleageindependentcut-point.Byagestratifying,sensitivityispreserved,whilespecificityisimprovedinelders,resultinginasignificantriseinpositivepredictivevalue,andashrinkingofthenumberof“greyzone”results.ThisapproachdoesnotimplythatNT-proBNPismoredependentonagethanisBNP;rather,byagestratifying,resultssuperiortothosefromBNPmaybegained.中国NT-proBNP诊断急性心力衰竭相关研究中国NT-proBNP诊断急性心力衰竭相关研究 中国近几年报道了十余篇NT-proBNP诊断急性心力衰竭的小样本研究 多数研究结果与国外PRIDE、ICON研究结果相仿，300ng/ml的排除截点可较好排除急性心力衰竭可能 国内对NT-proBNP诊断截点的研究尚未作过年龄分层研究和其它因素对截点影响的研究，目前十分需要进一步进行大样本的前瞻性观察，以提高临床鉴别诊断的效率。处理灰区值 灰区值定义为介于‘排除’(300ng/L)和按年龄调整的‘纳入’NT-proBNP值之间 按年龄分层比起单个截定点减少了灰区值的结果 在~20%的患者中仍然存在 了解造成NT-proBNP结果灰区值原因的鉴别诊断很重要AnothersituationthatmayoccurisanNT-proBNPthatfallsintothe“greyzone”.ThisisdefinedasanNT-proBNPvaluethatisbetweentheruleoutvalueof300ng/Landtheage-adjustedruleinvalue.Whileageadjustmentreducesthelikelihoodforagreyzoneresult,itisstillpresentinupto20%ofpatients.Inordertomanagethissituation,knowledgeofthedifferentialdiagnosisofagreyzoneNT-proBNPisimportant.NT-proBNP位于灰区时的鉴别诊断 冠状动脉缺血 心力衰竭病史 心肌疾病 左心室肥厚 限制性心肌病 心尖球形综合征 心肌炎 中毒,如化疗 心脏瓣膜病 心房颤动或扑动 先天性心脏病 肺心病 睡眠呼吸暂停 肺动脉栓塞 肺动脉高压 高排量(分流) 贫血 肾功能不全 严重疾病 细菌性败血症 烧伤 ARDS 卒中InlightofeverythingthatisknownaboutthetriggersforNT-proBNPandtheclinicalassociationswithNT-proBNPanddiseasestatesbesidesheartfailure,theclinicianthatemploysNT-proBNPtestingshouldknowthedifferentialdiagnosisforelevationofthismarkerincontextsotherthanheartfailure.Thisincludesmanycardiovasculardiagnoses,suchascoronaryischemia,heartmuscledisease,valvedisease,heartrhythmabnormalities,congenitalheartdisease,pulmonarydiseases,aswellasotherstateslesstypicallyassociatedwithcardiovasculardysfunction,suchasanemia,criticalillness,orstroke.Inallofthesesituations,irrespectiveofthereasonforNT-proBNPelevation,thismarkerhasbeenshowntobeprognosticallymeaningful.NT-proBNP诊断急性心力衰竭病史，体格检查，胸片，NT-proBNP检测患者入院时有急性呼吸困难Thus,ratherthanaone-step,“onesizefitsall”approachforuse,theoptimalwaytoconsiderNT-proBNPisasacontinuousvariable,acrosstheentirerangeofdiagnosticandprognosticpossibilities:forthosewithverylowvalues(e.g.<300ng/L)heartfailureisveryunlikelyandprognosisisexcellent,whileattheotherendofthespectrum,highervaluesareassociatedwithhigherlikelihoodforheartfailure,andworseoutcomes.Forthoseinthegreyzone,thecorrectdiagnosisofheartfailuredependsonclinicalcorrelation,andoutcomesareintermediate.NT-proBNP在急性心力衰竭预后评估中的应用NT-proBNP和预后在各心力衰竭阶段皆有预后价值的生物标志物…证据 COPERNICUS Val-HEFT PRIDE ICON GUSTO-IV,FRISC-II Richardsetal Kragelundetal HeartandSoul PEACE HOPE Zetheliusetal McKieetalIndeed,acrossthewiderangeofAHAstagesforheartfailure(StageA:atrisk,StageB:asymptomaticLVdysfunction,StageC:symptomaticHF,andStageD:endstageHF),NT-proBNPhasbeenshowntobepowerfullyprognostic.NT-proBNP>5000ng/ml提示心衰患者短期死亡率较高Januzzietal,EurHeartJ,2006;27:3300.850.900.951.00累计生存率P<.000010.700.750.80发作天数NT-proBNP<5,180ng/LNT-proBNP>5,180ng/LLogrankPvalue<.001Ofcourse,theearliestdatasupportingaprognosticroleforNT-proBNPwasinthosewithheartfailure.DefinitivedataontheutilityofNT-proBNPforshort-termmortalityriskinacutedecompensatedHFcamefromtheInternationalCollaborativeofNT-proBNPStudy,whereconcentrationsinexcessof5000ng/Lwereassociatedwithsignificantshort-termrisk.NT-proBNP>1000ng/ml提示心衰患者长期死亡率较高Januzzietal,ArchInternMed,(2006;166:315发作天数NT-proBNP<986ng/LNT-proBNP>986ng/L0100200300400发作天数NT-proBNP<986ng/LNT-proBNP>986ng/L0100200300400心力衰竭无心力衰竭LongertermassociationsbetweenNT-proBNPandoutcomesinthosewithacutedyspneawereestablishedinthePRIDEstudy,whereanNT-proBNP>1000ng/Lwasassociatedwithahigherlikelihoodforadverseoutcomeinthosewithandthosewithoutacuteheartfailure.NT-proBNP在急性心力衰竭治疗监测中的应用急性不稳性心衰治疗后NT-proBNP下降达30%是一个合理的目标Bettencourtetal,Circulation,2004;110:21681.00.80.60.40.20.0累计不住院生存降低>30%改变<30%升高>30%时间(天数)0100200SeenherearethedatafromBettencourtandcolleagues.Asdepicted,thosewhohadrobustreduction(>30%)intheirNT-proBNPconcentrationsaftertreatmentforacuteHFhadthebestoutcomes,whilethosewhoactuallyhadariseintheirvaluesduringtreatmenthadnearlyuniversaladverseoutcome,andthosewithintermediatechangeintheirNT-proBNPhad—aswouldbepredicted—intermediateoutcomes.急性非稳定性HF治疗后NT-proBNP的基线变化与其心血管事件风险成正比 有数据显示连续检测对于判断因HF住院预后的价值,但对于缺少缺少基线NT-proBNP值的患者 治疗后NT-proBNP值>4,137ng/L强烈预示较差的预后1 在此阈值以上每增加1000ng/L的NT-proBNP值,死亡或6个月内再入院的风险就增加8%1.Bayes-Genisetal,EurJHeartFail2004;6:3012.Bettencourtetal,Circulation2004;110:2168Ifserialmeasuresarenotavailable,apost-treatmentNT-proBNPofbelow~4000ng/Lisdesirable,astheriskfordeathorreadmissionrisesconsiderablyonceabovethisthreshold.NT-proBNP对急性非稳定性HF的治疗检测 NT-proBNP在住院时应检测2次：入院时和治疗后 急性不稳性心衰治疗后NT-proBNP下降达30%是一个合理的目标 如果没有测基线时NT-proBNP水平，对于急性期治疗的目标应为NT-ProBNP<4000ng/L 急性失代偿性HF患者病情好转时NT-proBNP仍升高，则说明其是高风险人群，建议考虑治疗是否充足，重新判断心衰的预后Asnoted,NT-proBNPshouldprobablyonlybemeasuredtwiceinthecourseofacuteHFhospitalization:atpresentationandafterperceivedsuccessfulmedicaltreatment.Adropof30%ormoreisdesirable(andifnopre-treatmentvalueisavailable,apost-treatmentlevelof<4000ng/Lisareasonablegoal).IncreaseinNT-proBNPaftertreatmentidentifiesaveryhighriskgroupinwhomspecifictherapeuticinterventionmightbewellapplied.现行心衰指南观点 2007中国慢性心力衰竭治疗指南：50岁以下的成人血浆NT-proBNP诊断急性心衰的截点为450pg/ml；50岁以上者的截点为900pg/ml；NT-proBNP＜300pg/ml为正常，可排除心衰。 2008年欧洲急性与慢性心衰诊疗指南：急性期测定NT-proBNP以排除心衰具有良好的阴性预测值；就诊时和出院前NT-proBNP水平增高具有重要的预后意义；NT-proBNP是拟诊急性心衰患者的建议流程中作为症状和体征基础上的5项一线检查之一 2010年AHA心衰指南：在急症室对心衰诊断尚未明确的患者，采用NT-proBNP检测进行评价是有用的；NT-proBNP检测也有助于患者的危险分层 2010年中国急性心力衰竭诊断治疗指南：NT-proBNP的浓度增高已成为公认诊断心衰的客观指标其临床意义①心衰的诊断和鉴别诊断②心衰的危险分层③评估心衰的预后：临床过程中这一标志物持续走高，提示预后不良NT-proBNP在急性心力衰竭中的应用 对于来急诊室就诊的急性呼吸困难患者，NTproBNP检测对排除和识别其中的急性心衰患者有较高的敏感性和特异性。但其最佳应用必须结合患者完整的病史、仔细的体格检查和有关NT-proBNP增高的鉴别诊断知识。 根据欧美资料，在急诊室，用于排除急性心衰的NT-proBNP水平为300pg/mL以下，其阴性预测值为98%。采用年龄分层的NT-proBNP诊断截点（50岁以下,50–75岁和75岁以上者分别为450、900和1,800pg/ml)可减少较年轻患者的假阴性结果和老年患者的假阳性结果，从而使总的阳性预测值得到改善而不改变总的敏感性和特异性，可供我国当前使用参考。我国患者的数据有待于进一步研究确定。小结与建议Inconclusion,NT-proBNPishighlysensitiveandspecificforthediagnosisandexclusionofacuteheartfailureindyspneicpatients,withresultsthatareatleastcomparabletoBNP.Whenappliedinalogicalfashion,NT-proBNPissuperiortoandadditivewithclinicaljudgmentfortheevaluationofacutedyspnea.TheoptimalapplicationofNT-proBNPisinthecontextofagoodclinicalevaluationtogetherwithknowledgeofcardiaccorrelatesofNT-proBNPelevationandagraspofthedifferentialdiagnosisofanelevatedNT-proBNP.NT-proBNP在急性心力衰竭中的应用 急性心衰患者就诊时的NT-proBNP水平具有重要的预后价值，治疗后的水平更有意义。因此推荐在基线时和治疗后作系列测定。 急性心衰治疗有效者T-proBNP水平迅速降低。虽然有关NT-proBNP检测对指导急性心衰治疗效果的前瞻性研究尚少，但观察性研究提示，急性心衰患者住院期间NTproBNP下降30％是一个合理的目标。 由于确定急性心衰恢复稳定的包括临床和生化指标，推荐在两个时间点测定NT-proBNP：基线或就诊时，以及病情达到稳定时，以确定是否可以出院，或是需要进一步加强治疗小结与建议Inconclusion,NT-proBNPishighlysensitiveandspecificforthediagnosisandexclusionofacuteheartfailureindyspneicpatients,withresultsthatareatleastcomparabletoBNP.Whenappliedinalogicalfashion,NT-proBNPissuperiortoandadditivewithclinicaljudgmentfortheevaluationofacutedyspnea.TheoptimalapplicationofNT-proBNPisinthecontextofagoodclinicalevaluationtogetherwithknowledgeofcardiaccorrelatesofNT-proBNPelevationandagraspofthedifferentialdiagnosisofanelevatedNT-proBNP.NT-proBNP在慢性心力衰竭中的应用 NT-proBNP在慢性心力衰竭诊断中的应用 NT-proBNP在慢性心力衰竭预后评估中的应用 NT-proBNP在慢性心力衰竭治疗监测中的应用Inthisstudy,followingenrollment,extensiveclinicaldatawerecollected,includingresultsofdiagnosticstudies.Inordertoascertainclinicalaccuracyforthediagnosisofheartfailure,themanagingEDphysicianwasasked—followingcompletionofevaluation—fortheirestimateofthepresenceofheartfailure.NT-proBNP在慢性心力衰竭诊断中的应用125pg/ml截点对有症状提示为心衰的患者具有很好的阴性预测值*Ageadjustedcutoffs1Zaphiriouetal,EurJHeartFail,2005;7:5372Nielsenetal,EurJHeartFail,2004;6:633Gustafssonetal,JCardFail,2005;11:S154Fuatetal,BrJGenPract,2006;56:3275Al-Barjasetal,EurJHeartFail,2004;3(suppl1):223StudiessuggestoptimalmodalityofuseforNT-proBNPinprimarycareistoharnessitsexcellentnegativepredictivevalue(NPV).Ingeneral,theoptimalrangetoruleoutHFissuggestedtobe100–160ng/L(NPV92%–100%),althoughsomedegreeofage-relateddifferenceincut-pointshasbeensuggested.NT-proBNP排除年轻慢性心衰患者的不同年龄截点 125pg/ml作为NT-proBNP单一截点的研究显示，其对有症状提示为心衰的患者具有很好的阴性预测值 对于年轻患者(<50岁),50ng/L的截点可能更有价值 对于中年患者(50–75之间),75ng/L是更好的截点Inyoungerpatients,asnoted,125ng/mLhasexcellentnegativepredictivevalue,whichmeansthatforyoungerpatientsbelowthisvalue,thelikelihoodforheartfailureisverylow.Breakingthedataoutinanevenmoregranularmanner,youngerpatients(suchasthose<50years)mightbebetterservedbyacut-pointof50ng/L,whileinmiddleagedpatients,acut-pointof75ng/Lmaybeevenmoreusefulthan125ng/L,howeverthesecut-pointsarenotyetproven.NT-proBNP排除老年慢性心衰患者的截点 80岁以上患者的截点建议为150ng/L1 采用125pg/ml作为截点来排除心衰很可能导致对大量老人启动进一步的心脏病学检查 美国FDA批准≥75岁者NT-proBNP截点为450pg/ml，可能不如＜250–300pg/ml有效21.Gustafssonetal,HeartDrug,2003;3:1412.Costello-Boerrigteretal,JAmCollCardiol,2006;47:345NT-proBNP125pg/ml作为慢性心衰排除的阴性截点值，不适合作为慢性心衰的诊断标准AsthemeanvalueofNT-proBNPineldersis150ng/L,itisobviousthatahighercut-pointforuseinthispopulationisneeded.Accordingly,ahighercut-pointof450ng/Lfortheelderlyhasbeenapproved,although250-300ng/Lmaybemoreusefulforthispopulationtoexcludeheartfailure.NT-proBNP在慢性心力衰竭预后评估中的应用NT-proBNP对慢性心力衰竭的预后评估 慢性HF的风险预测具有挑战性 传统预测风险的变量包括年龄，射血分数，肾功能和最大氧耗 与在急性HF中的预后评估相似，NT-proBNP浓度在慢性稳定性HF中是有力的不良预后的判断工具 NT-proBNP独立于多种其他风险因素，如年龄或射血分数TurningourattentiontotheapplicationofNT-proBNPtestingforprognosticationinchronicheartfailure,manyconsiderationsasinacuteheartfailureprognosisholdhereaswell.Firstoff—prognosticationinchronicheartfailuremaybechallenging,withmanypatientsdemonstratinghigherriskfeatures,buthavingratherbenigncourses.Traditionally,variablesusedtopredictriskincludeage,cardiacfunction,parametersofrenaldisease,aswellasmorecomplexdatapoints,suchasmaximaloxygenconsumption.Asinacuteheartfailureprognostication,NT-proBNPhasbeenroutinelyshowntobepowerfullyprognosticforadverseoutcomeinthosewithchronicstableheartfailure,aprognosticvaluethatisindependentofcovariatesofrisk.澳大利亚－新西兰心力衰竭研究小组：高NT-proBNP患者的长期死亡率和心衰发生率高于低NT-proBNP患者LowNT-proBNPHighNT-proBNPJAmCollCardiol2001;37:1781–1787.Val-HeFT研究：NT-proBNP越高的患者，其死亡、心衰住院的风险就越高ClinChem2006;52:1528–1538.Val-HeFT研究：NT-proBNP是心衰住院和死亡最强的预测因子ClinChem2006;52:1528–1538.COPERNICUS研究：NT-proBNP高于中位值患者的事件发生率高于NT-proBNP低于中位值患者一年事件率(%)allp=0.0001,logranktest6.222.416.440.319.941.933.952.8Circulation2004;110:1780–1786Onthisslide,1-yeareventratesofallendpointsarecomparedbetweenpatientswithNT-proBNPconcentrationsbelowandabovethemedian.LowNT-proBNPisindicatedingreen,highNT-proBNPinred.Forallendpoints,alldifferencesbetweentheeventratesofpts.withhighandlowNT-proBNPlevelswerehighlysignificant.Thisreferstomortalityaloneortodeathincombinationwithhospitalisationsduetoheartfailure,CVreasonsoranyreasons.COPERNICUS研究：NT-proBNP是最强的死亡和心衰住院的预测因子Circulation2004;110:1780–1786NT-proBNP的连续检测可更好判断慢性心衰患者预后04Months死亡率(%)因HF住院(%)NT-proBNP(pg/mL)Massonetal,JAmCollCardiol,2008;52:997Importantly,however,theVal-HeFTinvestigatorsthenexaminedthemeritsofsingleNT-proBNPmeasurementversusserialmeasurementsforriskpredictionandfoundthatserialmeasurementsovertimewereassociatedwithsuperiorriskstratificationcomparedtoasinglemeasurement.Whenevaluatingpatientswithtwoblooddrawsspaced4monthsapart,patientswhoeitherhadlowmeasurementsatbothblooddrawsortwohighmeasurementsatbothblooddrawshadpredictablylowandhighratesofadverseoutcome.However,patientswhostartedoutwithlowvalues(NT-proBNPbelow~1000pg/mL)butroseabovethisthresholdoverthe4monthsoffollowuphadworseoutcomesthanpatientswhostartedoutwithanNT-proBNPabove~1000pg/mLandfelloverthefollowupperiodofthestudy.ThisimpliesthatasignificantpercentageofpatientswouldbeincorrectlyassessedfortheirriskprofileifonlyonemeasurementofNT-proBNPwasmade.Furthermore,astherapiesforheartfailurehavedirecteffectsonconcentrationsofNT-proBNP,thetrendsovertimeofthismarkerinresponsetotherapeuticinterventionarelikelytoreflectprognosis.中国相关研究：发生终点事件者的血浆NT-proBNP水平中位数显著高于未发生终点事件的患者中国现代医药杂志2007；9（12）：1中国相关研究：NT-proBNP水平是预测心力衰竭终点事件的最强独立预测因子中国现代医药杂志2007；9（12）：1高NT-proBNP组心血管事件显著高于低NT-proBNP组中华检验医学杂志2006年29卷第1期27页NT-proBNP>301.1ng/mlNT-proBNP<301.1ng/mlNT-proBNP在慢性心力衰竭治疗监测中的应用TIME-CHF:NT-proBNP指导治疗 患者无心衰住院生存率显著改善(p=.01)患者无住院生存率显著改善(p=.02)患者死亡率显著改善(p=.01) Pfisterer.JAMA.2009;301(4):383-392N=622,15centerswhichenrolledpatients≥60yearsofage,NYHA≥IIwithelevatedNT-proBNP(≥400pg/mLif<75yearsofage,≥800pg/mLif≥75years)RandomizedtoNT-proBNPguidedtherapyorsymptom-guidedtherapy(SOC),followedfor18months.Endpoints:survivalfreeofanyhospitalizationandqualityoflifescore.PharmacologysupportwasesculatedtoattempttoreduceNT-proBNPvalues<400pg/mLif<75yearsofage,<800pg/mLif≥75years*TIME-CHF:对于<75岁患者，NT-proBNP指导治疗对于获益更多对于<75岁入选人群，NT-proBNP指导治疗组获益更为显著 心衰住院率降低(p=.002) 整体生存率提高(p=.02) 无住院生存率提高(p=.05) Age<75yPfisterer.JAMA.2009;301(4):383-392Figure6*BATTLESCARRED：NT-proBNP指导治疗相比常规治疗可更好降低患者死亡率死亡率(%)AthoughpatientsintheNT-proBNParmendedthetrialonhigherdosesofmedicationsoverall,theprimaryendpointofmortality,depictedhere,suggestedthattherewasnosignificantdifferencebetweentheclinicalandNT-proBNParms.BATTLESCARRED：对于<75岁患者，NT-proBNP指导治疗获益更多死亡率(%)*P=.048forNT-proBNPvsClinical†P=.02forNT-proBNPvsUsualcare*†However,whenconsideredasafunctionofage<75years(aprespecifiedendpoint),significantreductionsinmortalitywereobservedintheNT-proBNParms.PRIMA研究主要终点未出现显著差异PRIMAStudy：NT-proBNP治疗达标组患者无住院生存天数较临床指导治疗组延长9％Eurlings.2009ACC,oralpresentationEurlings.2009ACC,oralpresentationPRIMAStudyNT-proBNP治疗达标组患者死亡率较临床指导治疗组降低66％NT-proBNP治疗监测研究结果并不一致主要结果结果阳性阳性(<75y)阴性Blinding:Investigatorswillknowthesubject’sNT-proBNPtestresults,asknowledgeofthebiomarkerresultisintegraltotheexecutionoftheprotocolNT-proBNP在慢性心力衰竭中的应用 慢性心衰时血中NT-proBNP水平高于正常人和非心衰患者，但增高程度不及急性心衰。 用于门诊有症状的患者，建议125pg/ml以下作为“排除”心衰评价的截点，具有很好的阴性预测值。对50岁以下者，取＜50pg/ml可能更好；对50－75岁者，＜75–100pg/ml优于125pg/ml。高于年龄分层截点的NT-proBNP值并不一定说明存在心衰，往往需要作进一步的心血管检查。 NT-proBNP水平是慢性心衰各种临床终点最强的独立预测因素之一，并适用于不同程度的心衰患者。在慢性心衰，重复检测NT-proBNP更有助于判断远期预后，因此建议用于每一位患者的预后评价。小结与建议Inconclusion,NT-proBNPishighlysensitiveandspecificforthediagnosisandexclusionofacuteheartfailureindyspneicpatients,withresultsthatareatleastcomparabletoBNP.Whenappliedinalogicalfashion,NT-proBNPissuperiortoandadditivewithclinicaljudgmentfortheevaluationofacutedyspnea.TheoptimalapplicationofNT-proBNPisinthecontextofagoodclinicalevaluationtogetherwithknowledgeofcardiaccorrelatesofNT-proBNPelevationandagraspofthedifferentialdiagnosisofanelevatedNT-proBNP.NT-proBNP在慢性心力衰竭中的应用 用于门诊预后评定的NT-proBNP目标水平仍未定论。但心衰患者的终点事件发生率在NT-proBNP超过1,000pg/ml以上时显著增高。对门诊慢性心衰患者监测NT-proBNP，发现增高者有助于识别需要及时加强治疗的高危患者。 NT-proBNP治疗监测方面的研究结果并不一致。绝大多数治疗监测研究的入选患者已处于心衰终末期，疾病本身就有很高的病死率，这也是难以出现阳性结果的原因。我国尚未有NT-proBNP治疗监测方面的研究，建议今后能进行相关研究。小结与建议 NT-proBNP作为慢性心衰诊断的标准值需要确定，有助于指导心衰的临床诊断，该共识中没有确定，以125pg/m以下截点不能作为心衰的诊断指标 采用NT-proBNP心衰阴性截点值排除心衰，指导基础心脏病进一步检查，不符合心衰临床诊断路径Inconclusion,NT-proBNPishighlysensitiveandspecificforthediagnosisandexclusionofacuteheartfailureindyspneicpatients,withresultsthatareatleastcomparabletoBNP.Whenappliedinalogicalfashion,NT-proBNPissuperiortoandadditivewithclinicaljudgmentfortheevaluationofacutedyspnea.TheoptimalapplicationofNT-proBNPisinthecontextofagoodclinicalevaluationtogetherwithknowledgeofcardiaccorrelatesofNT-proBNPelevationandagraspofthedifferentialdiagnosisofanelevatedNT-proBNP.NT-proBNP的影响因素及其参考值BNP/NT-proBNP临床应用注意事项哪些病理生理因素会导致NP的升高心室壁受压、牵拉及心肌缺血——拮抗RAAS/SNS其他伴随着心内压力增高的所有心脏条件（许多concomitantdisease）在很大程度上影响两种利钠肽，干扰对结果的解释——要针对每一位病人具体分析。检测时的影响因素NT-proBNP分析前注意事项 标本采集：无需固定体位和时间，但要避免剧烈运动（心率提高50%）——其基本不受体位改变和日常活动影响，且不存在日间、天间的生理学波动。月经周期对NP没有显著的影响。建议1）抽血前静息10-15分钟，最好固定采血体位。2）采血前要考虑治疗药物的影响。 标本选择:选择血清/血浆（包括肝素、EDTA抗凝）/POCT方法还可用全血——EDTA抗凝血浆较血清或肝素血浆检测结果低10%-13%。建议：使用血清。NT-proBNP分析前注意事项 临床治疗的影响：要考虑治疗药物的影响。在血流动力学稳定的情况下/体积负荷最小时，才能客观地评价心功能状态。由于BNP具有利钠、利尿、扩血管、拮抗肾素-血管紧张素-醛固酮系统（RAAS）和交感神经系统（SNS）的作用。所以，凡是参与促进这一神经内分泌轴激活的激素，如肾上腺素、糖皮质激素、甲状腺素，都会引起BNP/NT-proBNP水平的升高。同样，这些激素的拮抗剂及可使这些激素降低的药物，如ACE-I抑制剂、β-受体阻滞剂、肾上腺素拮抗剂和利尿剂等会使BNP/NT-proBNP浓度降低。另外，沙坦类、胺碘酮也会使其降低，而洋地黄类药物会使其升高。NT-proBNP检测不会受人类重组BNP（nesiritide）分子治疗的影响NT-proBNP分析中注意事项 由于NT-proBNP只有一个抗体及标准品来源(Roche)，其分析的一致化应不存问题