心力衰竭的诊断与治疗面临的选择与挑战

心力衰竭的诊断与治疗：,面临的选择与挑战,内容,脑钠肽、N端脑钠肽前体在心力衰竭诊断和处理中的地位他汀类药物治疗心力衰竭力不从心？,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。,BNP100but500HFlikely,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,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,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,Richardsetal.JAmCollCardiol2006;47:5260,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1620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并无临床价值，治疗1W后BNP才出现明显变化,AmJCardiol2004;93:1562-1563AmJCardiol2008;101:3A,病人因急性呼吸困难来急诊,病史采集,体格检查,ECG,胸片+NTproBNP,充血性心力衰竭高度不可能,充血性心力衰竭高度可能,充血性心力衰竭不可能？可能？其他检查,NTproBNP450pg/mL-病人900pg/mL-病人50-75岁1800pg/mL病人75岁,Bayes-GenisA.RevEspCardiol2005,灰色区域中心力衰竭的独立预测因子,vanKimmenade,etal,AJC,2006,AcuteHeartFailure-BNPlevelsandriskstratificationfromtheEDtodischarge,UNDER100HEARTFAILUREUNLIKELYCAUSEOFSOB,UNDER250PATIENTISATLOWRISKANDMAYBEDISCHARGEDSAFELY,CONSIDERBNPINTHECONTEXTOFCLINICALSYMPTOMS,ABOVE600pg/mlPATIENTISCONSIDEREDSTILLATHIGHRISK,EDADMISSIONINPATIENTDISCHARGEARRIVAL(Tiime),1,500,600,250,100,BNPValues(pg/ml),600pg/ml,400/pg/ml,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,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,VanKimmenadeetal.JACC2006,多种标志物检测:+GFR,联合传统标志物，NT-proBNP预后价值加强,BNP药理作用：治疗急性失代偿性心衰,扩血管（vasodilator）利钠（natriuretic）利尿（diuretic）抗纤维化（antifibrotic）Nesiritide（natrecor）,Fitzgerald,ACC2004,BNP:-治疗过程中明显升高，不能反应体内分泌BNP浓度-治疗结束后2小时才低于基线NT-proBNP-治疗中12小时即可以明显低于基线水平，反映治疗效果-治疗结束24小时可以达到最大程度的降低,在接受奈西立肽治疗的心衰患者中对BNP和NT-proBNP变化的监测,12hrs,24hrsInfusion,JourdainPetaletal.JACC2007;49:1733-9,BNP的监测指导治疗:STARS-BNP多中心研究,BNP/NT-proBNP可以指导治疗吗?,内容,脑钠肽、N端脑钠肽前体在心力衰竭诊断和处理中的地位他汀类药物治疗心力衰竭力不从心？,BeneficialEffectsofStatins,Anti-InflammatoryEffectsAntioxidantEffectsEndothelialFunctionEffectsonAngiogenesisCardiacHypertrophyandLVRemodelingNeurohormonalActivation,JAmCollCardiol.2008;51(4),StatinsandRisksforDeathandHeartFailureHospitalisationin25,000heartfailurepatients,GoAetal.JAMA2006;296:21052111,0,5,10,15,20,25,30,35,Rateper100person-years,BaselineCHD,NoBaselineCHD,Overall,RateofDeath,No.,24598,19705,4893,0,5,10,15,20,25,30,35,BaselineCHD,NoBaselineCHD,Overall,RateofHospitalization,No.,24598,19705,4893,NoStatin,Statin,Adjustedmortalityamongpatientswithischemicetiology(n=62,273),Mortalityamongpatientswithheartfailureofnonischemicetiology(n=31,551),A,B,既往的研究结果使人们对他汀治疗心衰充满希望然而，这些试验只是产生假说的初步研究他汀类能否进一步用于临床的心衰治疗,尚需要开展大规模的前瞻性研究率先完成的是CORNOA试验,Patients(n=5011)ChronicischaemicsystolicheartfailurereceivingoptimalHFtreatment(diuretics,ACEinhibitors,ARBs,beta-blockertherapy)Ejectionfraction0.40(NYHAclassIII/IV)or0.35(NYHAclassII)60years,rosuvastatin10mg(n=2514),placebo(n=2497),Endpoints:Timetocardiovasculardeath,non-fatalMI,non-fatalstrokeTotalmortality,Visit:Week:,18to2,24to2,30,46,5213monthly,Final3y,ARandomized,Double-Blind,Placebo-ControlledStudywithRosuvastatininPatientswithChronicSymptomaticSystolicHeartFailure,CORONA-StudyDesign,EligibilityOptimalHFtreatmentinstituted,Medianfollow-up2.7years,Placeborun-in,KjekshusJetal.EurJHeartFail2005;7:1059-1069,Meanage(years)737375years(%)4141Femalesex(%)2424NYHAclass(%)II3737III6261IV1.61.4EjectionFraction0.310.31Myocardialinfarction(%)6060Anginapectoris(%)7273CABGorPCI(%)2626Hypertension(%)6363,PlaceboRosuvastatinn=2497n=2514,CORONA-Baselinecharacteristics,KjekshusJetal.NEngJMed2007;357doi10.1056/NEJMoa0706201,Totalcholesterol(mmol/L)5.355.36LDLcholesterol(mmol/L)3.563.54hsCRP,median(mg/L)3.53.5Looporthiazidediuretic(%)8889Aldosteroneantagonist(%)3939ACEinhibitor(%)8080Beta-blocker(%)7575Antiplateletoranticoagulant(%)9090,PlaceboRosuvastatinn=2497n=2514,CORONA-MedicalHistory,KjekshusJetal.NEngJMed2007;357doi10.1056/NEJMoa0706201,-50,-40,-30,-20,-10,0,10,LDL-C,HDL-C,TG,CRP,CORONAEffectsonLDL-C,HDL-C,TGandCRPat3months;Absolutedifferencebetweenrosuvastatinandplacebo,Betweengroupdifferencefrombaseline(%),45%,5.0%,20.5%,37.1%,p0.001,p0.001,p0.001,p0.001,KjekshusJetal.NEngJMed2007;357doi10.1056/NEJMoa0706201,CORONA-PrimaryEndpointThecombinedendpointofcardiovasculardeathornon-fatalMIornon-fatalstroke(timetofirstevent),Hazardratio=0.9295%CI0.83to1.02p=0.12,Monthsoffollow-up,0,36,30,24,18,12,6,Placebo,Rosuvastatin10mg,No.atriskPlacebo249723152156200318511431811Rosuvastatin251423452207206819321484855,Percentofpatientswithprimaryendpoint,KjekshusJetal.NEngJMed2007;357doi10.1056/NEJMoa0706201,Monthsoffollow-up,0,36,30,24,18,12,6,Placebo,Rosuvastatin10mg,0,3,6,12,9,15,Hazardratio=0.8495%CI0.70to1.00p=0.05,No.atriskPlacebo249723152156200318511431811Rosuvastatin251423452207206819321484855,DataonFile,CORONAPosthocanalysisofthenumberfatal/non-fatalMIorstrokeintheprimaryendpoint,Percentofpatientswithevent,p=0.01,p=0.007,p0.001,4,074,2,464,1,299,1,510,3,694,2,193,1,109,1,501,0,1,000,2,000,3,000,4,000,Heartfailure,Allcause,CVcause,Non-CVcause,Placebo(n=2,497),Rosuvastatin10mg(n=2,514),CORONA-SecondaryEndpointsTotalnumberofhospitalizations,No.hospitalisations,KjekshusJetal.NEngJMed2007;357doi10.1056/NEJMoa0706201,对CORONA试验的解释,入选患者平均年龄达73岁，63%患者的NYHA心功能为和级。试图通过改变粥样硬化自然史，影响心血管罹患率和死亡率的作用可能有限在CORONA试验的亚组分析中，发现对于那些心衰程度轻，一般状况良好的年轻患者，他汀更能凸显其优势。或他汀在年龄相对较年轻的轻度心衰患者中可能会得到不同的结果。同一类药物不等于同一种药物。还不能确定CORONA研究的局限是瑞舒伐他汀本身的问题,还是他汀类治疗老年心衰患者无确切疗效。,对CORONA试验的思考,当我们仔细思考慢性心衰的病理生理基础时，就能容易理解CORONA的结果。他汀类药物是“一类神奇的药