正常射血分?jǐn)?shù)心力衰竭HF-PEF診斷和治療進(jìn)展.ppt

正常射血分?jǐn)?shù)心力衰竭(HF-PEF)診斷和治療進(jìn)展解放軍總醫(yī)院李小鷹,定義,左室收縮功能代償性心衰(preservedleftventricularejectionfraction,PLVEF）左心室射血分?jǐn)?shù)正常心力衰竭(heartfailurewithpreservedejectionfraction，HF-PEF）包括：（1）舒張性心力衰竭、（2）急性二尖瓣返流、主動(dòng)脈瓣返流、（3）其他原因的循環(huán)充血狀態(tài)。,有充血性心力衰竭典型的表現(xiàn)（肺循環(huán)和體循環(huán)淤血）非心臟瓣膜病靜息時(shí)伴異常的舒張性功能不全收縮功能正?；騼H有輕微減低,舒張性心力衰竭（diastolicheartfailure,DHF）,由于這些患者通常表現(xiàn)為典型的心力衰竭癥狀，因此應(yīng)當(dāng)將其歸類(lèi)到C期。孤立的舒張功能不全少見(jiàn)，通常伴有不同程度的收縮功能不全。,舒張性心力衰竭的病因與病理生理特點(diǎn),HF-PEF的主要病因和誘發(fā)因素,老年人，女性心房顫動(dòng)高血壓伴左心室肥厚肺部感染糖尿病腎功能不全冠心病心肌缺血貧血肥胖限制性和浸潤(rùn)性心肌病,HF-PEF患者有高血壓的比例,大多數(shù)HF-PEF患者有高血壓大多數(shù)既往或目前有LVH,1.SenniMetal.Circulation.1998;98:2282-2289.4.OwanTEetal.NEnglJMed.2006;355:251-2592.VasanRSetal.JAmCollCard.1999;33:1948-1955.5.BhatiaRSetal.NEnglJMed.2006;355:260-2693.GottdienerJSetal.AnnInternMed.2002;137:631-639,Framingham2,Olmsted1,CHS3,Owan4,Bhatia5,37,36,170,60,59,78,880,1570,2167,2429,n=,患者(%),n=CHF患者總?cè)藬?shù),55,63,59,75,58,49,48,57,71,50,0,20,40,60,80,100,EF尚正常,EF降低,從危險(xiǎn)因素到心力衰竭,吸煙高脂血癥糖尿病高血壓,心梗,左室肥厚,收縮功能不良,舒張功能不良,心力衰竭(收縮性與舒張性）,左室結(jié)構(gòu)和功能正常,左室重構(gòu),無(wú)癥狀左室功能不良,癥狀性心力衰竭,年,年/月,Levyetal.JAMA,275:1557,1996,Normal,SystolicHeartFailure,DiastolicHeartFailure,Aurigemma,Zile,GaaschCirculation2005,HF-PEF的發(fā)病機(jī)制和主要病理生理環(huán)節(jié)左心室向心性重構(gòu),左心室舒張功能障礙血管-心室硬度增大，擴(kuò)張儲(chǔ)備功能降低左心室長(zhǎng)軸收縮功能減退對(duì)運(yùn)動(dòng)的心率變時(shí)效應(yīng)減弱RAS和交感神經(jīng)系統(tǒng)激活,HF-PEF患者主動(dòng)脈可擴(kuò)張性降低,HundleyWG,etal.JAmCollCardiol.2001;38:796-802.,PicogramsperMililiter,Controls,SHF,DHF,Controls,SHF,DHF,Controls,SHF,DHF,Norepinephrine,BrainNatriureticPeptide,C-TerminalAtrialNatriureticPeptide,Kitzman,etal.JAMA.2002;288:2144-2150.,神經(jīng)內(nèi)分泌功能:SHF,isolatedDHFandcontrols,2500,2000,1500,1000,500,0,900,800,500,400,100,0,700,600,200,300,500,450,300,250,50,0,400,350,100,200,150,左心室功能不全的壓力/容積機(jī)制,左心室壓力,左心室容積,舒張功能不全高血壓高齡左心室肥厚向心性重構(gòu),收縮功能不全心梗、心肌病、容量負(fù)荷過(guò)重高血壓離心性重構(gòu),ZileMR,BrutsaertDL.Circulation.2002;105;1387-1393.,左心室舒張功能不全的進(jìn)程,高血壓老齡動(dòng)脈粥樣硬化糖尿病,血管肥厚彈力蛋白和膠原改變鈣化內(nèi)皮功能不全順應(yīng)性喪失,心肌肥厚纖維化/膠原改變凋亡心梗/缺血細(xì)胞功能不全順應(yīng)性喪失，舒張受損,心力衰竭,死亡、心梗、急性冠脈綜合征、心衰、心律失常、卒中,1.ZileMR,BrutsaertDL.Circulation.2002;105;1503-1508;2.KassDA,etal.CirculationRes.2004;94:1533-1542.,舒張性心功能不全發(fā)病率及預(yù)后,心力衰竭患病率,66-103,75-86,70-84,75,50,40,25,55-95,78,76,75,60,68,65,年齡段,平均年齡,美國(guó)(CHS),芬蘭(Helsinki),英國(guó)(Poole),丹麥.(Copen.),西班牙(Asturias),葡萄牙(EPICA),荷蘭(Rotter.),瑞典(Vasteras),左心室收縮功能降低的比例,HF-PSF的比例,55,51,68,46,71,59,39,71,PetrieM,McMurrayJ.Lancet.2001;358:423-434.HoggKetal.JAmCollCard.2004;43:317-327.,CHF患病率(%),0,1,2,3,4,5,6,7,8,9,10,心力衰竭患者中HF-PEF的比例,EF50%,EF45%,EF50%,EF50%,Framingham2(n=73),Olmstead1(n=137),CHS3(n=269),NHFProject4(n=19,710),1.SenniMetal.Circulation.1998;98:2282-2289.2.VasanRSetal.JAmCollCard.1999;33:1948-1955.3.GottdienerJSetal.AnnInternMed.2002;137:631-639.,EF50%,EF50%,Owan5(n=4,596),Bhatia6(n=2,802),Patients(%),4.MasoudiFAetal.JAmCollCard.2003;41-217-223.5.OwanTEetal.NEnglJMed.2006;355:251-259.6.BhatiaRSetal.NEnglJMed.2006;355:260-269.,HF-PEF患病趨勢(shì),OwanTEetal.NEnglJMed.2006;355:251-259.,HF-PEF的死亡率,OwanTEetal.NEnglJMed.2006;355:251-259;BhatiaRSetal.NEnglJMed.2006;355:260-269.,1yearmortality,29,32,22.2,25.5,SHF與HF-PEF的預(yù)后(5年生存率)OWANTEetal.NEnglJMed2006;355:251-259,射血分?jǐn)?shù)正常的患者,射血分?jǐn)?shù)降低的患者,危險(xiǎn)病例數(shù),危險(xiǎn)病例數(shù),年,年,生存率,生存率,心力衰竭患者的再住院率,HoggKetal.JAmCollCard.2004;43:317-327.,診斷要點(diǎn),+,+,收縮性HF(SHF)與HF-PEF:癥狀與體征,GivertzMMetal.In:BraunwaldE,ZipesDP,LibbyP,eds.HeartDisease,7thedition.Philadelphia,Pa:WBSaunders.2001;534-561.,ESC2005年建議舒張性心功能不全需同時(shí)滿(mǎn)足以下的三個(gè)必要條件充血性心力衰竭的癥狀和體征。左室收縮功能正常或僅有輕度異常。左室松弛、充盈、舒張期擴(kuò)張能力異?；蚴鎻埰诮┯驳淖C據(jù)。,美國(guó)心臟病學(xué)會(huì)和美國(guó)心臟病協(xié)會(huì)（AHA/ACC）建議的診斷標(biāo)準(zhǔn)：,有典型的心力衰竭癥狀和體征，同時(shí)超聲心動(dòng)圖顯示患者左心室射血分?jǐn)?shù)正常并且沒(méi)有瓣膜疾?。ㄈ缰鲃?dòng)脈狹窄或二尖瓣返流）。AHH/ACC2005年慢性心力衰竭診治指南,中國(guó)舒張性心力衰竭診斷標(biāo)準(zhǔn)（2007指南）,有典型心衰的癥狀和體征；LVEF正常（45%），左心腔大小正常；UCG有左室舒張功能異常的證據(jù)；UCG檢查無(wú)瓣膜病，心包疾病及肥厚或限制型心肌病。,舒張性心力衰竭的診斷標(biāo)準(zhǔn),YturraldeRFandGaaschWH.ProgCardiovascDis2005;47:314-319.KorensteinDetal.BMCEmergMed2007;7:6,HF-PEF診斷步驟(ESC共識(shí),2007),HF的癥狀或體征,LVEF50%且左心室舒張末期容積指數(shù)(LVEDVI)12mmHg或左心室舒張末壓16mmHg,組織多普勒,NTproBNP220pg/mlBNP200pg/ml,E/E15,15E/E8,超聲血流多普勒:.E/ADT.肺靜脈血流.左房擴(kuò)大.左心室肥厚.房顫,NTproBNP220pg/mlorBNP200pg/ml,HFNEF,組織多普勒E/E8,FromPaulus.EurHeartJ.2007,輔助檢查,超聲心動(dòng)圖射血分?jǐn)?shù)：45%舒張功能不全。二尖瓣血流頻譜:E/AIVRT(等容舒張時(shí)間)EDT(E峰減速時(shí)間),三種異常的左室充盈模式：松弛受損型：輕度舒張功能異常，E峰下降A(chǔ)峰增高，EA減小。假性正?；溆褐卸仁鎻埞δ墚惓?。EA和減速時(shí)間正常。限制型充盈模式：重度舒張功能異常E峰升高及減速時(shí)間縮短，EA顯著增大。,左心室舒張功能超聲心動(dòng)圖分析,HoCYetal.Circulation.2006;113:e396-398e.,TheHongKongDiastolicHeartFailureStudy,NormalDHFp-valueNumber38151Female/Male24/1493/58Age(years)7277470.11IVSd(cm)0.30.001LVEDD(cm)0.70.001LVESD(cm)0.70.068FS(%)3663280.0.005LVEF2d(%)62867100.12LVmass(g)21161305940.001LAD(cm)0.70.001E(m/s)0.670.20.650.20.52A(m/s)0.790.20.920.20.0005E/A0.30.0005DT(ms)20063259770.0005IVRT(ms)1001811732危險(xiǎn))控制血壓(證據(jù)水平:A)控制房顫患者的心室率(C)利尿劑控制肺淤血或外周水腫(C)IIa級(jí)(益處危險(xiǎn))冠心病患者冠脈再通術(shù)對(duì)舒張功能的效應(yīng)(C)IIb級(jí)(益處危險(xiǎn))房顫患者轉(zhuǎn)復(fù)為竇律(C)使用阻滯劑、ACEI、ARB或CCB良好控制血壓以減輕心衰癥狀(C)地高辛減輕心衰癥狀(C),Huntetal.JAmCollCardiol.2005:46;e1-e82.,HF-PEF治療推薦HeartFailureSocietyofAmericaPracticeGuideline(2006),低鈉飲食C容量過(guò)度負(fù)荷患者使用噻嗪類(lèi)或襻利尿劑C使用ARBs或ACEIsARBs:B,ACEI:C合并冠心病或糖尿病患者使用ACEIs或ARBsC使用阻滯劑心肌梗死史A高血壓B需要控制心室率的心房顫動(dòng)B使用CCBdiltilzem或verapamil用于阻滯劑不能耐受的心房顫動(dòng)C心絞痛癥狀A(yù)高血壓C,AdamsKF,etal.JCardFail2006;12:10-38,CHARM-added,CHARM-preserved,CHARM研究,坎地沙坦在癥狀性心衰患者的研究,CHARM-alternative,n=2028LVEF18歲的癥狀性心力衰竭患者3023例(NYHA分級(jí)IIIV),左心室射血分?jǐn)?shù)40%隨訪(fǎng)和主要終點(diǎn)主要終點(diǎn):心血管死亡或因心力衰竭住院.平均隨訪(fǎng)36.6月治療安慰劑或坎地沙坦,劑量逐漸增加到32mg,每天一次,YusufSetal.Lancet2003;362:777-781.,CHARM研究,NumberatRisk,NumberatRisk,Candesartan,Placebo,Candesartan,Placebo,CHARM-PreservedPrimaryoutcome:CVdeathorCHFhospitalisation,YusufSetal.Lancet.2003;362:777781.,NumberatriskCandesartan151414581377833182Placebo150914411359824195,CVdeath,CHFhosp.333366-CVdeath170170-CHFhosp.241276CVdeath,HFhosp,365399MICVdeath,HFhosp,388429MI,strokeCVdeath,HFhosp,460497MI,stroke,revasc,candesartanbetter,Hazardratio,placebobetter,0.8,1.0,1.2,p-value,0.918,0.072,0.118,0.126,0.078,0.123,Covariateadjustedp-value,0.635,0.047,0.051,0.051,0.037,0.13,Candesartan,Placebo,0.89,0.99,0.85,0.90,0.88,0.91,CHARM-PreservedPrimaryandsecondaryoutcomes,YusufSetal.Lancet2003;362:777-781.,PEP-CHF:培哚普利治療老年人心力衰竭,入選標(biāo)準(zhǔn):年齡70歲最近6個(gè)月內(nèi)因心衰住院臨床診斷HF利尿劑治療舒張功能不全的證據(jù)隨機(jī):,培哚普利2mg,安慰劑,n=426,n=424,平均隨訪(fǎng)2.2年主要研究終點(diǎn):全因死亡或心力衰竭住院,ClelandJG.EurHeartJ.2006;27:2338-2345.,HFhospitalization,Cleland,etal.EurHeartJ.2006;27:2338-2345.,DeathandHFhospitalization,3,70,69,Placebo,3,PEP-CHF:EffectofperindoprilinHF-PEFpatients,VALIDDValsartanInDiastolicDysfunction:EffectoftheAngiotensinIIAntagonistValsartanonDiastolicFunctioninPatientswithHypertensionandDiastolicDysfunction,ScottD.Solomon,RajeshJanardhanan,AnilVerma,MikhailBourgoun,YvesLaCourcier,StephenHippler,WilliamA.Kaye,HaroldFields,TasneemZ.Naqvi,WilliamL.Daley,SusanRitter,SharonMulvagh,J.MalcolmO.Arnold,MichaelZile,JamesD.Thomas,GerardP.AurigemmafortheVALIDDStudyInvestigators,StudyDesign,MenandWomen45yrsoldHistoryoforNewlyDiagnosedHypertensionPreservedEjectionFraction(50%)EvidenceofDiastolicDysfunction:(byDTI:age45-55,E10cm/s;age55-65,E9cm/s;age65+E8cm/s),Valsartan320mgqd(plusStandardAntihypertensiveTherapy)n=186,Non-RAAS(plusStandardAntihypertensiveTherapy)n=198,PrimaryEndpoint:ChangeinDiastolicMyocardialrelaxationvelocity(E),baselineto9monthsSecondaryEndpoints:IVRT,S,DT,LVMass,BloodPressureTreatedtoatargetof135/80inbotharmsutilizingamenuofconcomitantmedications(diuretics,betaorcalcium-channelblockers,alphablockers)excludingRAASinhibitors,Randomization,Multi-center,randomized,placebocontrolled,double-blindtrial,n=