NproBNP在心衰診療預(yù)后治療的管理專家講座

N-proBNP在心衰診療、預(yù)后、治療管理

廣東省人民醫(yī)院心內(nèi)科廣東省心血管病研究所

陳魯原NproBNP在心衰診療預(yù)后治療的管理專家講座第1頁(yè)

內(nèi)容NT-proBNP在心力衰竭患者診療中應(yīng)用NT-proBNPinthediagnosisofdefiniteheartfailureNT-proBNP判斷心衰預(yù)后及對(duì)治療反應(yīng)NT-proBNPinthejudgemenofprognosisofheartfailure應(yīng)用NT-proBNP指導(dǎo)急性失代償性心竭治療

NT-proBNPandTherapyMonitoringforAcutelyDestabilizedHFNproBNP在心衰診療預(yù)后治療的管理專家講座第2頁(yè)在初級(jí)保健中被誤診為心力衰竭百分比：

-Framingham: 40%(McKee1971)

-Boston: 42%(Carlson1985)

-Kuopio: 50%(Remes1991)急診室中25-50%失代償心力衰竭病人被誤診充血性心力衰竭:在臨床上是否易于診療?三大癥狀非特異性（氣促、踝腫和疲勞）,尤其對(duì)于肥胖、老年和婦女。心衰體征僅提醒心衰存在，但仍需有心功效評(píng)價(jià)客觀證據(jù)。NproBNP在心衰診療預(yù)后治療的管理專家講座第3頁(yè)Independentpredictorsofacuteheartfailureindyspneicpatientsintheemergencydepartment急診室呼吸困難患者急性心力衰竭獨(dú)立預(yù)測(cè)原因ElevatedNT-proBNP

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

胸片間質(zhì)水腫11.04.5-26.0<.0001Orthopnea端坐呼吸9.64.0-23.0<.0001Loopdiureticuseatpresentation

就診時(shí)應(yīng)用袢利尿劑3.41.8-6.4.01Ralesonpulmonaryexamination肺部羅音2.41.2-5.2.05Age(peryear)年紀(jì)1.031.01-1.05.01Cough咳嗽0.430.23-0.83.05Fever發(fā)燒0.170.05-0.50.03JanuzziJL,Jr.,AmJCardiol

NproBNP在心衰診療預(yù)后治療的管理專家講座第4頁(yè)

診療心衰三大常規(guī)

胸片是心衰初步診療主要部分心臟超聲是現(xiàn)在“金標(biāo)準(zhǔn)”

（仍不能完全處理急性呼吸困難判別問(wèn)題）到當(dāng)前為止，由美國(guó)和歐洲心臟病協(xié)會(huì)推薦使用BNP或NT-proBNP是唯一用于診療心力衰竭試驗(yàn)室檢測(cè)指標(biāo)胸片、心臟超聲和BNP/NT-proBNP檢測(cè)是診療心衰三大常規(guī)NproBNP在心衰診療預(yù)后治療的管理專家講座第5頁(yè)NT-proBNP年紀(jì)分層降低了假陽(yáng)性和假陰性，提升了陽(yáng)性預(yù)測(cè)值ICON三重界值無(wú)需依據(jù)腎功效對(duì)NT-proBNP界值深入調(diào)整83%55%92%73%85%1800pg/ml全部>75歲(n=519)86%66%88%84%90%總計(jì)85%88%82%82%90%900pg/ml全部50-75歲(n=554)95%99%76%93%97%450pg/ml全部<50歲(n=183)準(zhǔn)確度陰性預(yù)測(cè)值陽(yáng)性預(yù)測(cè)值特異性敏感性適當(dāng)界值年紀(jì)分層Januzzi,etal,EurHeartJAnwaruddin,etal,JACC,診療急性心力衰竭國(guó)際氨基末端腦鈉肽原幫助數(shù)據(jù)依據(jù)年紀(jì)分層NT-proBNP“診療”界值NproBNP在心衰診療預(yù)后治療的管理專家講座第6頁(yè)NT-proBNP和BNP

對(duì)有癥狀并疑診為心衰患者診療路徑臨床檢驗(yàn)，心電圖，胸部X線，超聲心動(dòng)圖利鈉肽慢性心衰不可能慢性心衰可能不確定ESC心衰指南

EurHeartJ;29:2388-2442腦鈉肽在心衰診療中有著主要地位NproBNP在心衰診療預(yù)后治療的管理專家講座第7頁(yè)BNP和NT-proBNP檢測(cè)分析NT-proBNP半衰期相對(duì)較長(zhǎng)，濃度相對(duì)較穩(wěn)定，含量相對(duì)較高（比BNP約高16～20倍），檢測(cè)相對(duì)較輕易，是較理想預(yù)測(cè)標(biāo)志物BNP半衰期相對(duì)較短，（18分鐘），檢測(cè)血液時(shí)間要求高；在了解病人即刻情況時(shí)較有價(jià)值BNP或NT-proBNP臨床應(yīng)用價(jià)值基本相同天天或隔天檢測(cè)BNP/NT-proBNP并無(wú)臨床價(jià)值，治療1W后才出現(xiàn)顯著改變AmJCardiol;93:1562-1563AmJCardiol;101:3ANproBNP在心衰診療預(yù)后治療的管理專家講座第8頁(yè)NT-proBNP用于急性呼吸困難患者

診療灰色地帶值A(chǔ)lthoughagestratificationofNT-proBNPcut-pointsfortheevaluationofpatientswithacutedyspneareducesthelikelihoodofagreyzonevalue,thisfindingwasstillpresentin17%ofsubjectsintheICONstudy盡管臨床工作中推薦采取NT-proBNP切點(diǎn)標(biāo)準(zhǔn)年紀(jì)分層方式可提升心衰診療水平，但依然有17%患者NT-proBNP仍處于灰色地帶值A(chǔ)mJCardiol;101:3ANproBNP在心衰診療預(yù)后治療的管理專家講座第9頁(yè)DiagnosesassociatedwithanintermediateNT-proBNPconcentrationbutwithoutacuteheartfailureascauseoftheirdyspneainICON.

ICON研究中NT-proBNP中度升高但無(wú)急性心力衰竭患者呼吸困難原因

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

肺炎/支氣管炎12(12%)Acutecoronarysyndrome/chestpainACS/胸痛12(12%)Arrhythmia/bradycardia

心律失常/心動(dòng)過(guò)緩8(8%)Lungcancer(includingmetastases)

肺癌（含轉(zhuǎn)移性）5(5%)Anxietydisorder

焦慮狀態(tài)5(5%)Pulmonaryemboli

肺栓塞3(3%)Pulmonaryhypertension

肺動(dòng)脈高壓1(1%)Pericarditis

心包炎1(1%)Other*其它21(21%)Unknown

原因不明19(19%)vanKimmenadeRRJ.AmJCardiol

對(duì)NT-proBNP灰度值并不代表良性預(yù)測(cè),更不能認(rèn)為其為陰性結(jié)果NproBNP在心衰診療預(yù)后治療的管理專家講座第10頁(yè)體征OR95%CIp-value咳嗽0.180.06-0.520.001利用袢利尿劑3.991.58-10.10.003夜間陣發(fā)性呼吸困難4.501.32-15.40.02頸靜脈怒張3.051.06-8.790.04心力衰竭前2.631.02-6.800.05下肢水腫2.960.94-9.310.06第三心音奔馬律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喘鳴0.810.29-2.220.17

‘灰色區(qū)域’中心力衰竭獨(dú)立預(yù)測(cè)因子

當(dāng)NT-proBNP400－pg/ml時(shí)，主要依據(jù)臨床判斷vanKimmenade,etal,AJC,NproBNP在心衰診療預(yù)后治療的管理專家講座第11頁(yè)

內(nèi)容NT-proBNP在心力衰竭患者診療中應(yīng)用NT-proBNPinthediagnosisofdefiniteheartfailureNT-proBNP判斷心衰預(yù)后及對(duì)治療反應(yīng)NT-proBNPinthejudgemenofprognosisofheartfailure應(yīng)用NT-proBNP指導(dǎo)急性失代償性心竭治療

NT-proBNPandTherapyMonitoringforAcutelyDestabilizedHFNproBNP在心衰診療預(yù)后治療的管理專家講座第12頁(yè)急性心力衰竭,5000pg/ml是短期預(yù)后界值

判斷急性心力衰竭短期（60天）預(yù)后NproBNP在心衰診療預(yù)后治療的管理專家講座第13頁(yè)Januzzietal.ArchInternMed

判斷急性心力衰竭長(zhǎng)久（1年）預(yù)后對(duì)于1年危險(xiǎn)度分層，最正確界值是1000pg/mlNproBNP在心衰診療預(yù)后治療的管理專家講座第14頁(yè)NT-proBNPandTherapyMonitoringforAcutelyDestabilizedHF

急性不穩(wěn)定性心力衰竭NT-proBNP監(jiān)測(cè)

SincecriteriafordeterminingrestabilizationfromdestabilizedHFincludeclinicalfactorsaswellasbiochemicalmeasures,thefrequencyofNT-proBNPmeasurementshouldbeoptimallyappliedattwotimepoints:baseline/presentation因?yàn)闆Q定不穩(wěn)定性心力衰竭到病情穩(wěn)定包含臨床原因和生化指標(biāo)，NT-proBNP檢測(cè)頻率應(yīng)該在兩個(gè)時(shí)間點(diǎn)進(jìn)行：基線/入院時(shí)（用于診療、篩查及設(shè)定治療“起點(diǎn)”），和病情穩(wěn)定時(shí)，以決定是否可出院或治療程度NproBNP在心衰診療預(yù)后治療的管理專家講座第15頁(yè)NT-proBNPinacuteHFDias2001000Survivalwithoutreadmissions

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

p<0.0001BettencourtP.CirculationNproBNP在心衰診療預(yù)后治療的管理專家講座第16頁(yè)對(duì)急性失代償性心衰住院患者治療反應(yīng)檢測(cè)AlthoughprospectivestudiesontheeffectofNT-proBNPmeasurementinguidingtherapyinacutedestabilizedHFarelacking,observationaldatasuggestthata30%decreaseinNT-proBNPvaluesduringhospitalizationforacutedestabilizedHFisareasonablegoal.IfabaselinemeasureofNT-proBNPisnotavailable,aNT-proBNPlevel<4000pg/mlafteracutetreatmentisdesirable.盡管缺乏關(guān)于檢測(cè)NT-proBNP指導(dǎo)缺血性心臟病治療前瞻性研究,觀察性研究表明急性心衰病人經(jīng)治療后NT-proBNP水平降低30%是合理，假如不能提供基線NT-proBNP水平，治療后小于4000pg/ml是理想水平NproBNP在心衰診療預(yù)后治療的管理專家講座第17頁(yè)AlgorithmforuseofNT-proBNPduringhospitalizationforacuteHF

急性心力衰竭住院期間NT-proBNP應(yīng)用流程

NproBNP在心衰診療預(yù)后治療的管理專家講座第18頁(yè)

NT-proBNP與慢性性心衰預(yù)后在慢性心衰患者中，NT-proBNp是與臨床終點(diǎn)相關(guān)最強(qiáng)獨(dú)立預(yù)測(cè)因子之一AmongpatientswithchronicHF,repeateddeterminationsofNT-proBNPlevelsappeartoconveyadditionalprognosticvalueforrelevantadverseoutcomes,includingdeathordestabilizationofHFrequiringhospitalization,andarethusrecommendedateachpatientevaluation.（在慢性心衰患者中重復(fù)檢測(cè)NT-proBNP，能夠提供獨(dú)特臨床不良事件預(yù)測(cè)，比如死亡、因?yàn)樾乃夯偃朐旱?，故推薦在評(píng)價(jià)每個(gè)心衰患者時(shí)使用。）NproBNP在心衰診療預(yù)后治療的管理專家講座第19頁(yè)

NT-proBNP與慢性性心衰預(yù)后Targetvaluesforoutpatientprognosticationremainrelativelyundefined.However,theriskformorbidityandmortalityinHFappearstoincreasemarkedlywithanNT-proBNPconcentration>1000pg/ml.門診病人靶目標(biāo)水平仍未確定，但NT-proBNP水平大于1000pg/ml，則心衰發(fā)病和死亡率顯著上升NproBNP在心衰診療預(yù)后治療的管理專家講座第20頁(yè)

內(nèi)容NT-proBNP在心力衰竭患者診療中應(yīng)用NT-proBNPinthediagnosisofdefiniteheartfailureNT-proBNP判斷心衰預(yù)后及對(duì)治療反應(yīng)NT-proBNPinthejudgemenofprognosisofheartfailure應(yīng)用NT-proBNP指導(dǎo)急性失代償性心竭治療

NT-proBNPandTherapyMonitoringforAcutelyDestabilizedHFNproBNP在心衰診療預(yù)后治療的管理專家講座第21頁(yè)

檢測(cè)NT-proBNP能指導(dǎo)

急性失代償性心衰住院患者治療嗎？NT-proBNPlevelsdecreaseinresponsetotheadditionoftherapieswithprovenbenefitforHF,includingACE-inhibitors,angiotensinreceptorblockers,diuretics,spironolactone,exercisetherapyandbiventricularpacing.已往已經(jīng)證實(shí)有益心衰冶療（包含ACEI、血管擔(dān)心素受體阻滯劑、利尿劑、安體舒通、運(yùn)動(dòng)療法和雙心室腔起搏）均可降低NT-proBNP水平NproBNP在心衰診療預(yù)后治療的管理專家講座第22頁(yè)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.;301(4):383-392NproBNP在心衰診療預(yù)后治療的管理專家講座第23頁(yè)

ACEIorARBand-BlockerDosesDuringtheStudyTherewerenosignificantdifferencesbetweenthe2treatmentgroupsbyBNPlevel(P=.30).JAMA.;301(4):383-392TIME-CHFNproBNP在心衰診療預(yù)后治療的管理專家講座第24頁(yè)TIME-CHF:PrimaryandSecondary

OutcomesJAMA.;301(4):383-392hospitalization-freesurvival(p=0.46),but↓inCHFNproBNP在心衰診療預(yù)后治療的管理專家講座第25頁(yè)Greaterreductionsinpatientsyoungerthan75yearsJAMA.;301(4):383-392Age≤75yrAge≥75yrNproBNP在心衰診療預(yù)后治療的管理專家講座第26頁(yè)NT-proBNPguidedmanagement

ofchronicheartfailurebasedon

an

individual

targetvalue

PRIMA-studyLucEurlings,StudyCoordinatorMaastrichtUniversityMedicalCenterMaastricht,theNetherlandsYigalPinto,PrincipalInvestigatorAcademicMedicalCenterAmsterdam,theNetherlandsACCCongressOrlandoMarch29th

NproBNP在心衰診療預(yù)后治療的管理專家講座第27頁(yè)P(yáng)RIMA-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-study

MainoutcomeACCOrlandoMarchNproBNP在心衰診療預(yù)后治療的管理專家講座第28頁(yè)P(yáng)RIMA-studyNumberofincreasesHFmedicationNT-proBNPClinicalP

n174171

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

MainoutcomeACCOrlandoMarchNproBNP在心衰診療預(yù)后治療的管理專家講座第29頁(yè)TotalMortalityPRIMA-studySurvival(%)Time(days)P=0.208NT-proBNPguidedClinicalguided46/17426.5%57/17133.3%NproBNP在心衰診療預(yù)后治療的管理專家講座第30頁(yè)SecondaryanalysisPRIMA-studyCardiovascularmortality nsCombinedendpointCVmortality/readmissions nsHFrelatedreadmissions nsCreatinineabove/belowthemedian(123mcm/L) nsAgeabove/below73years nsDischargeNT-proBNPabove/below2950pg/ml nsNproBNP在心衰診療預(yù)后治療的管理專家講座第31頁(yè)OnNT-proBNPtargetanalysis:PrimaryendpointPRIMA-studyOnNT-proBNPTargetClinicalGuidedgroup院外平均存活天數(shù)(median+IQR)721(578-730)p<.001664(435-726)101of174patientsinNT-proBNPguidedgroup(58%)

maintainedtheirtargetinmorethan75%ofvi