NproBNP在心衰诊断预后治疗的管理

NproBNP在心衰诊断预后治疗的管理第1页/共35页规范与指南

NT-proBNP临床应用中国专家共识

ExpertconsensusofclinicalapplicationofNT－proBNPNT-proBNP临床应用中国专家共识小组

【关键词】脑钠肽；Ｎ末端Ｂ型利钠肽原；心力衰竭；心血管疾病

【Ｋeywords】ＢＮＰ；ＮＴ－ｐｒｏＢＮＰ；Ｈｅａｒｔｆａｉｌｕｒｅ；Ｃａｒｄｉｏｖａｓｃｕｌａｒｄｉｓｅａｓｅ

doi：10.3969/j．issn．1672－5301．2011．06．001

中图分类号Ｒ541；Ｑ516文献标识码Ａ文章编号1672-5301(2011)06-0401-08第2页/共35页在初级保健中被误诊为心力衰竭的比例：

-Framingham: 40%(McKee1971)

-Boston: 42%(Carlson1985)

-Kuopio: 50%(Remes1991)急诊室中25-50%的失代偿心力衰竭病人被误诊充血性心力衰竭:在临床上是否易于诊断?三大症状非特异性（气促、踝肿和疲劳）特别对于肥胖、老年和妇女。心衰体征仅提示心衰存在但仍需有心功能评价的客观证据。第3页/共35页

急诊室呼吸困难患者急性心力衰竭的独立预测因素

IndependentpredictorsofacuteheartfailureindyspneicpatientsintheemergencydepartmentElevatedNT-proBNP

NT-proBNP升高44.021.0-91.0<.0001InterstitialedemaonchestX-ray

胸片间质水肿11.04.5-26.0<.0001Orthopnea

端坐呼吸9.64.0-23.0<.0001Loopdiureticuseatpresentation

就诊时应用袢利尿剂3.41.8-6.4.01Ralesonpulmonaryexamination

肺部罗音2.41.2-5.2.05Age(peryear)

年龄1.031.01-1.05.01Cough

咳嗽0.430.23-0.83.05Fever

发热0.170.05-0.50.03JanuzziJL,Jr.,AmJCardiol2005第4页/共35页

诊断心衰的三大常规

胸片是心衰初步诊断的重要部分心脏超声是现在的“金标准”

（仍不能完全解决急性呼吸困难的鉴别问题）到目前为止，由美国和欧洲心脏病协会推荐使用的BNP或NT-proBNP是唯一用于诊断心力衰竭的实验室检测指标胸片、心脏超声和BNP/NT-proBNP检测是诊断心衰的三大常规第5页/共35页

NT-proBNP年龄分层降低了假阳性和假阴性，提高了阳性预测值

ICON的三重界值无需根据肾功能对NT-proBNP界值进一步调整83%55%92%73%85%1800pg/ml所有>75岁(n=519)86%66%88%84%90%总计85%88%82%82%90%900pg/ml所有50-75岁(n=554)95%99%76%93%97%450pg/ml所有<50岁(n=183)精确度阴性预测值阳性预测值特异性敏感性合适界值年龄分层Januzzi,etal,EurHeartJ2005Anwaruddin,etal,JACC,2006诊断急性心力衰竭国际氨基末端脑钠肽原协助数据根据年龄分层的NT-proBNP“诊断”界值第6页/共35页NT-proBNP和BNP

对有症状并疑诊为心衰患者的诊断路径临床检查，心电图，胸部X线，超声心动图利钠肽慢性心衰不可能慢性心衰可能

不确定2008ESC心衰指南

EurHeartJ2008;29:2388-2442脑钠肽在心衰诊断中有着重要的地位第7页/共35页BNP和NT-proBNP的检测分析NT-proBNP半衰期相对较长，浓度相对较稳定，含量相对较高（比

BNP约高16～20倍），检测相对较容易，是较理想的预测标志物BNP半衰期相对较短，（18分钟），检测血液时间要求高；在了解病人即刻情况时较有价值BNP或NT-proBNP的临床应用价值基本相同每天或隔天检测BNP/NT-proBNP并无临床价值，治疗1W后才出现明显变化AmJCardiol2004;93:1562-1563AmJCardiol2008;101:3A第8页/共35页NT-proBNP用于急性呼吸困难患者

诊断的灰色地带值AlthoughagestratificationofNT-proBNPcut-pointsfortheevaluationofpatientswithacutedyspneareducesthelikelihoodofagreyzonevalue,thisfindingwasstillpresentin17%ofsubjectsintheICONstudy尽管临床工作中推荐采用NT-proBNP切点标准的年龄分层方式可提高心衰的诊断水平，但仍然有17%患者的NT-proBNP仍处于灰色地带值AmJCardiol2008;101:3A第9页/共35页DiagnosesassociatedwithanintermediateNT-proBNPconcentrationbutwithoutacuteheartfailureascauseoftheirdyspneainICON.

ICON研究中NT-proBNP中度升高但无急性心力衰竭患者的呼吸困难原因

DiagnosisPatients(n=99)Chronicobstructivepulmonarydisease/asthmaCOPD/哮喘12(12%)Pneumonia/bronchitis

肺炎/支气管炎12(12%)Acutecoronarysyndrome/chestpainACS/胸痛12(12%)Arrhythmia/bradycardia

心律失常/心动过缓8(8%)Lungcancer(includingmetastases)

肺癌（含转移性）5(5%)Anxietydisorder

焦虑状态5(5%)Pulmonaryemboli

肺栓塞3(3%)Pulmonaryhypertension

肺动脉高压1(1%)Pericarditis

心包炎1(1%)Other*

其他21(21%)Unknown

原因不明19(19%)vanKimmenadeRRJ.AmJCardiol2006对NT-proBNP灰度值并不代表良性预测,更不能认为其为阴性结果第10页/共35页体征OR95%CIp-value咳嗽0.180.06-0.520.001利用袢利尿剂3.991.58-10.10.003夜间阵发性呼吸困难4.501.32-15.40.02颈静脉怒张3.051.06-8.790.04心力衰竭前2.631.02-6.800.05下肢水肿2.960.94-9.310.06第三心音奔马律10.40.82-130.70.07COPD/哮喘前0.480.20-1.190.11端坐呼吸2.060.73-5.830.17喘鸣0.810.29-2.220.17

‘灰色区域’中心力衰竭的独立预测因子

当NT-proBNP400－2000pg/ml时，主要根据临床判断vanKimmenade,etal,AJC,2006第11页/共35页

内容NT-proBNP在心力衰竭患者诊断中的应用

NT-proBNPinthediagnosisofdefiniteheartfailureNT-proBNP判断心衰预后及对治疗的反应

NT-proBNPinthejudgemenofprognosisofheartfailure应用NT-proBNP指导急性失代偿性心竭的治疗

NT-proBNPandTherapyMonitoringforAcutelyDestabilizedHF第12页/共35页急性心力衰竭,5000pg/ml

是短期预后的界值

判断急性心力衰竭短期（60天）预后第13页/共35页Januzzietal.ArchInternMed2006

判断急性心力衰竭长期（1年）预后对于1年危险度的分层，最佳界值是1000pg/ml第14页/共35页

急性不稳定性心力衰竭的NT-proBNP监测

NT-proBNPandTherapyMonitoringforAcutelyDestabilizedHFSincecriteriafordeterminingrestabilizationfromdestabilizedHFincludeclinicalfactorsaswellasbiochemicalmeasures,thefrequencyofNT-proBNPmeasurementshouldbeoptimallyappliedattwotimepoints:baseline/presentation由于决定不稳定性心力衰竭到病情稳定包括临床因素和生化指标，NT-proBNP的检测频率应该在两个时间点进行：基线/入院时（用于诊断、筛查及设定治疗的“起点”），和病情稳定时，以决定是否可出院或治疗程度。第15页/共35页NT-proBNPinacuteHFDays2001000Survivalwithoutreadmissions

1,00,80,60,40,20,0Decrease30%Within<30%Increase30%

p<0.0001BettencourtP.Circulation2004第16页/共35页对急性失代偿性心衰住院患者治疗反应的检测AlthoughprospectivestudiesontheeffectofNT-proBNPmeasurementinguiding

therapyinacutedestabilizedHFarelacking,observationaldatasuggestthata30%

decreaseinNT-proBNPvaluesduringhospitalizationforacutedestabilizedHFisa

reasonablegoal.IfabaselinemeasureofNT-proBNPisnotavailable,aNT-proBNP

level<4000pg/mlafteracutetreatmentisdesirable.尽管缺少关于检测NT-proBNP指导缺血性心脏病治疗的前瞻性研究,观察性研究表明急性心衰病人经治疗后NT-proBNP水平降低30%是合理的，如果不能提供基线NT-proBNP水平，治疗后小于4000pg/ml是理想水平第17页/共35页

急性心力衰竭住院期间的NT-proBNP应用流程

AlgorithmforuseofNT-proBNPduringhospitalizationforacuteHF第18页/共35页

NT-proBNP与慢性性心衰的预后在慢性心衰患者中，NT-proBNp是与临床终点相关的最强的独立预测因子之一AmongpatientswithchronicHF,repeateddeterminationsofNT-proBNP

levelsappeartoconveyadditionalprognosticvalueforrelevantadverse

outcomes,includingdeathordestabilizationofHFrequiringhospitalization,

andarethusrecommendedateachpatientevaluation.

（在慢性心衰患者中反复检测NT-proBNP，能够提供独特的临床不良事件的预测，例如死亡、因为心衰恶化再入院等，故推荐在评价每个心衰患者时使用。）第19页/共35页

NT-proBNP与慢性性心衰的预后

Targetvaluesforoutpatientprognosticationremainrelativelyundefined.However,theriskformorbidityandmortalityinHFappearstoincreasemarkedlywithanNT-proBNPconcentration>1000pg/ml.门诊病人的靶目标水平仍未确定，但NT-proBNP水平大于1000pg/ml，则心衰的发病和死亡率明显上升第20页/共35页

内容NT-proBNP在心力衰竭患者诊断中的应用

NT-proBNPinthediagnosisofdefiniteheartfailureNT-proBNP判断心衰预后及对治疗的反应

NT-proBNPinthejudgemenofprognosisofheartfailure应用NT-proBNP指导急性失代偿性心竭的治疗

NT-proBNPandTherapyMonitoringforAcutelyDestabilizedHF第21页/共35页

检测NT-proBNP能指导

急性失代偿性心衰住院患者的治疗吗？NT-proBNPlevelsdecreaseinresponsetotheadditionoftherapieswithprovenbenefitforHF,includingACE-inhibitors,angiotensinreceptorblockers,diuretics,

spironolactone,exercisetherapyandbiventricularpacing.已往已经证明有益的心衰冶疗（包括ACEI、血管紧张素受体阻滞剂、利尿剂、安体舒通、运动疗法和双心室腔起搏）均可降低NT-proBNP水平第22页/共35页TheTrialofIntensifiedvsStandardMedicalTherapy

inElderlyPatientsWithCongestiveHeartFailure

(TIME-CHF)design:PatientswithchronicsystolicHFwererandomizedtointensifiedBNP-guidedtherapyorstandardtherapyPatients:499patientswithsystolicheartfailure≤EF45%,NYHAII–IV,priorhospitalizationforHF≤1year,andBNPlevel≥400pg/mLin≤75yrand≥800pg/mLin≥75yrClinicaloutcomeswerecomparedat18months.

Primaryoutcomes:18-monthsurvivalfreeofall-causeHo-spitalizationsandqualityoflifeJAMA.2009;301(4):383-392第23页/共35页

ACEIorARBand-BlockerDosesDuringtheStudyTherewerenosignificantdifferencesbetweenthe2treatmentgroupsbyBNPlevel(P=.30).JAMA.2009;301(4):383-392TIME-CHF第24页/共35页

TIME-CHF:PrimaryandSecondary

Outcomes

JAMA.2009;301(4):383-392hospitalization-freesurvival(p=0.46),but↓inCHF第25页/共35页Greaterreductionsinpatientsyoungerthan75yearsJAMA.2009;301(4):383-392Age≤75yrAge≥75yr

TIME-CHF:PrimaryandSecondary

Outcomes

第26页/共35页NT-proBNPguidedmanagement

ofchronicheartfailurebasedon

an

individual

targetvalue

PRIMA-studyLucEurlings,StudyCoordinatorMaastrichtUniversityMedicalCenterMaastricht,theNetherlandsYigalPinto,PrincipalInvestigatorAcademicMedicalCenterAmsterdam,theNetherlandsACCCongressOrlandoMarch29th2009第27页/共35页PRIMA-studyProspective,randomized,single-blindedstudyAdmittedwithsymptomaticheartfailure;

ElevatedNT-proBNPlevels≥1,700pg/mlonhospitaladmissionNT-proBNPguidedTreatmentIndividualNT-proBNPtargetlevel(Lowestlevelatdischargeor2weeksfollow-up)ClinicalguidedTreatmentFollow-upat2weeks,1,3,6,9,12,15,21,24months;Follow-upupminimal1yearPRIMA-studyMainoutcomeACCOrlandoMarch2009第28页/共35页PRIMA-studyNumberofincreasesHFmedicationNT-proBNPClinicalP

n174171

Diuretics1681200.018Betablockers10595nsACE-inhibitors77550.099AT-IIantagonists4122nsAldosteronantagonists1915nsDigoxin1419nsTotal4243260.006PRIMA-study

MainoutcomeACCOrlandoMarch2009第29页/共35页TotalMortalityPRIMA-studySurvival(%)Time(days)P=0.208NT-proBNPguided

Clinicalguided46/17426.5%57/17133.3%第30页/共35页SecondaryanalysisPRIMA-studyCardiovascularmortality nsCombinedendpointCVmortality/readmissions nsHFrelatedreadmissions nsCreatinineabove/belowthemedian(123mcm/L) nsAgeabove/below73years nsDischargeNT-proBNPabove/below2950pg/ml ns第31页/共35页OnNT-proBNPtargetanalysis:Primar