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

正常射血分?jǐn)?shù)心力衰竭(HF-PEF)

診斷和治療進(jìn)展

定義2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、主動脈瓣返流、（3）其他原因的循環(huán)充血狀態(tài)。3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)將其歸類到C期。孤立的舒張功能不全少見，通常伴有不同程度的收縮功能不全。5舒張性心力衰竭的病因與

病理生理特點(diǎn)6HF-PEF的主要病因和誘發(fā)因素

老年人，女性▲心房顫動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性心肌病7

從危險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)無癥狀左室功能不良癥狀性心力衰竭年年/月

Levyetal.JAMA,275:1557,19969NormalSystolicHeartFailureDiastolicHeartFailureAurigemma,Zile,GaaschCirculation200510HF-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)張儲備功能降低

左心室長軸收縮功能減退對運(yùn)動的心率變時效應(yīng)減弱

RAS和交感神經(jīng)系統(tǒng)激活

11PicogramsperMililiterControlsSHFDHFControlsSHFDHFControlsSHFDHFNorepinephrineBrainNatriureticPeptideC-TerminalAtrialNatriureticPeptideKitzman,etal.JAMA.2002;288:2144-2150.神經(jīng)內(nèi)分泌功能:

SHF,isolatedDHFandcontrols25002000150010005000900800500400100070060020030050045030025050040035010020015013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)荷過重高血壓離心性重構(gòu)ZileMR,BrutsaertDL.Circulation.2002;105;1387-1393.14左心室舒張功能不全的進(jìn)程高血壓老齡動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;94:1533-1542.15心力衰竭患病率66-10375-8670-847550>40>2555-9578–7675–606865年齡段平均年齡美國(CHS)芬蘭(Helsinki)英國(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5551684671593971PetrieM,McMurrayJ.Lancet.2001;358:423-434.HoggKetal.JAmCollCard.2004;43:317-327.CHF患病率(%)01234567891017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%EF>50%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;355:260-269.1819HF-PEF的死亡率

OwanTEetal.NEnglJMed.2006;355:251-259;BhatiaRSetal.NEnglJMed.2006;355:260-269.1yearmortality293222.225.521SHF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)降低的患者危險病例數(shù)危險病例數(shù)年年生存率生存率22心力衰竭患者的再住院率

HoggKetal.JAmCollCard.2004;43:317-327.Readmissionrates(%)PhilbinetalMalkietalSmithetalDautermanetalHeartfailurewithpreservedsystolicfunction(HF-PEF)44264658Systolicheartfailure(SHF)4233465823參數(shù)SHFHF-PSF病史冠心病高血壓糖尿病瓣膜性心臟病陣發(fā)性呼吸困難+++++++++++++++++++++—+++體格檢查心界擴(kuò)大心音低鈍S3奔馬律S4奔馬律高血壓瓣膜返流啰音水腫頸靜脈充盈+++++++++++++++++++++++++++++++++++++++胸部X線(X-ray)心臟擴(kuò)大肺淤血+++++++++++++++++

++++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;534-561.25

ESC

2005年建議舒張性心功能不全

需同時滿足以下的三個必要條件充血性心力衰竭的癥狀和體征。左室收縮功能正?；騼H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)。26舒張性心力衰竭的診斷標(biāo)準(zhǔn)

YturraldeRFandGaaschWH.ProgCardiovasc

Dis2005;47:314-319.KorensteinDetal.BMCEmergMed2007;7:6主要標(biāo)準(zhǔn)1.臨床心衰證據(jù)弗萊明翰標(biāo)準(zhǔn)(2個主要或1個主要＋2個次要標(biāo)準(zhǔn))波士頓標(biāo)準(zhǔn)(5-7分:可能HF;

8-12分:確診HF)血漿BNP升高(>400pg/ml3)

或胸部X-線示肺淤血心肺運(yùn)動試驗示肺功能減弱2.LVEF及心腔大小正常3.左心室舒張、充盈異常，舒張期僵硬明確證據(jù)1.左心室肥厚或向心性重構(gòu)2.

左房擴(kuò)大(無房顫)3.多普勒超聲心動圖或?qū)Ч軝z查有舒張功能不全的證據(jù)29HF-PEF診斷步驟(ESC共識,2007)

HF的癥狀或體征LVEF>50%且左心室舒張末期容積指數(shù)(LVEDVI)

<97ml

/

m2左心室舒張、充盈、舒張期擴(kuò)脹和硬度異常肺動脈楔壓>12mmHg或左心室舒張末壓>16mmHg組織多普勒NTproBNP>220pg/mlBNP>200pg/mlE/E’>1515>E/E’>8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NTproBNP>220pg/mlorBNP>200pg/mlHFNEF組織多普勒E/E’>8FromPaulus.EurHeartJ.200730輔助檢查31

超聲心動圖射血分?jǐn)?shù)：>45%舒張功能不全。二尖瓣血流頻譜:E/A

IVRT(等容舒張時間)EDT(E峰減速時間)32三種異常的左室充盈模式：①松弛受損型：輕度舒張功能異常，E峰下降A(chǔ)峰增高，E／A減小。②假性正?；溆褐卸仁鎻埞δ墚惓！／A和減速時間正常。③限制型充盈模式：重度舒張功能異常E峰升高及減速時間縮短，E／A顯著增大。

33左心室舒張功能超聲心動圖分析HoCYetal.Circulation.2006;113:e396-398e.34TheHongKongDiastolicHeartFailureStudy

NormalDHFp-valueNumber38151Female/Male24/1493/58Age(years)72±774±70.11IVSd(cm)1.2±0.21.4±0.30.001LVEDD(cm)4.4±0.54.9±0.70.001LVESD(cm)2.9±0.53.4±0.70.068FS(%)36±632±80.0.005LVEF2d(%)62±867±100.12LVmass(g)211±61305±94<0.001LAD(cm)3.4±0.44.1±0.7<0.001E(m/s)0.67±0.20.65±0.20.52A(m/s)0.79±0.20.92±0.2<0.0005E/A0.9±0.30.7±0.3<0.0005DT(ms)200±63259±77<0.0005IVRT(ms)100±18117±32<0.0005E/Em12±320±9<0.0005YipGWKetal.Heart2008;94:57335

心電圖：可發(fā)現(xiàn)心房顫動及其它心律失常；心肌梗死、缺血征象；左室肥厚征象;PtfV1負(fù)值增大。血漿心房肽和腦鈉肽：高于正常血漿水平提示心力衰竭。36胸片：

肺瘀血、肺水腫，心臟大小正?；蛐呐K略擴(kuò)大。核醫(yī)學(xué)檢查、心導(dǎo)管與冠脈造影檢查等

37舒張性心力衰竭

治療原則3806年AHA/ACC對舒張性心力衰竭患者的治療建議

建議分類證據(jù)級別*

醫(yī)師應(yīng)當(dāng)根據(jù)發(fā)表的指南控制收縮期和舒張期高血壓IA*醫(yī)師應(yīng)當(dāng)控制心房顫動患者的心室率IC*醫(yī)師應(yīng)當(dāng)使用利尿劑控制肺充血和周圍性水腫IC*冠狀動脈疾病患者有癥狀性或可證實(shí)的心肌缺血對心臟舒張功能有不利影響時，最好行冠狀動脈重建治療IIaC*心房顫動患者恢復(fù)并維持竇性心律可能有助于改善癥狀I(lǐng)IbC*高血壓患者應(yīng)用β受體阻滯劑、ACEI、ARB或鈣拮抗劑，可能有助于最大程度緩解癥狀I(lǐng)IbC*應(yīng)用洋地黃來最大程度減輕心力衰竭癥狀的價值尚不清楚IIbC39

HF-PSF治療建議(ACC/AHA,2005)I級(益處>>>危險)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(益處>>危險)冠心病患者冠脈再通術(shù)對舒張功能的效應(yīng)(C)IIb級(益處≥危險)房顫患者轉(zhuǎn)復(fù)為竇律(C)使用β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.證據(jù)水平A資料來源于多中心、隨機(jī)臨床研究或薈萃分析結(jié)果B資料來源于單中心隨機(jī)臨床研究或非隨機(jī)研究C僅僅是專家意見、病例研究或臨床實(shí)踐的共識40HF-PEF治療推薦HeartFailureSocietyofAmericaPracticeGuideline(2006)■低鈉飲食C■容量過度負(fù)荷患者使用噻嗪類或襻利尿劑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β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B■使用CCB

diltilzem或verapamil用于β阻滯劑不能耐受的心房顫動C心絞痛癥狀A(yù)高血壓CAdamsKF,etal.JCardFail2006;12:10-3841CHARM-addedCHARM-preserved

CHARM研究坎地沙坦在癥狀性心衰患者的研究CHARM-alternativen=2028

LVEF<40%

不能耐受ACEIn=2548LVEF<40%

一直使用ACEIn=3025LVEF>40%

使用或不使用ACEIPrimaryoutcomeforoverallprogram:All-causedeathPrimaryoutcomeforeachtrial:CVdeathorHFhospitalizationHF,heartfailure;LVEF,leftventricularejectionfraction.PfefferMAetal.Lancet.2003;362:759-766.單獨(dú)使用ARBACEI+ARB有或無ACEI+ARB42CHARM-Preserved目的驗證ARB坎地沙坦能否使左心室收縮功能尚存的慢性心力衰竭患者受益設(shè)計多國多中心、隨機(jī)、雙盲、安慰劑對照試驗患者年齡>18歲的癥狀性心力衰竭患者3023例(NYHA分級II–IV),左心室射血分?jǐn)?shù)>40%隨訪和主要終點(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;362:777-781.43CHARM研究NumberatRiskNumberatRiskCandesartanPlaceboCandesartanPlacebo單獨(dú)使用ARB組1013101583179843442712212692988710131015831798434427122126929887504000233.5Time(Years)3020101504000233.5Time(Years)3020101PlaceboCandesartanProportionwithCVDeathororHospitalizationforCHF23%RR,p=0.0004ACEI+ARB組12761272106310139489064574221176113612761272106310139489064574221176113650400Time(Years)302010233.510233.51PlaceboCandesartanProportionwithCVDeathororHospitalizationforCHF15%RR,p=0.01左室舒張功能不全組1514150913771359833824182195145814411514150913771359833824182195145814410233.5Time(Years)10233.5Time(Years)1PlaceboCandesartanProportionwithCVDeathororHospitalizationforCHF11%RR,p=0.12504003020105040030201044CHARM-Preserved

Primaryoutcome:

CVdeathorCHFhospitalisation0123years3.50102030PlaceboCandesartan51525HR0.89(95%CI0.77-1.03),p=0.118

AdjustedHR0.86,p=0.051

%366(24.3%)333(22.0%)YusufSetal.Lancet.2003;362:777–781.NumberatriskCandesartan1514

1458

1377

833 182Placebo

1509

1441

1359

824

19545CVdeath,CHFhosp.

333

366

-CVdeath

170

170

-CHFhosp.

241

276CVdeath,HFhosp,

365

399

MI CVdeath,HFhosp,

388

429

MI,stroke

CVdeath,HFhosp,

460

497

MI,stroke,revasc

candesartan

betterHazardratioplacebo

better0.81.01.2p-value0.9180.0720.1180.1260.0780.123Covariateadjusted

p-value0.6350.0470.0510.0510.0370.13CandesartanPlacebo0.890.990.850.900.880.91CHARM-Preserved

PrimaryandsecondaryoutcomesYusufSetal.Lancet2003;362:777-781.46PEP-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=426n=424

平均隨訪2.2年主要研究終點(diǎn):全因死亡或心力衰竭住院ClelandJG.EurHeartJ.2006;27:2338-2345.47HFhospitalizationCleland,etal.EurHeartJ.2006;27:2338-2345.DeathandHFhospitalization37069Placebo3PEP-CHF:

EffectofperindoprilinHF-PEFpatientsPt.atriskPerindoprilPlacebo012424426374356184186Perindopril1yr=HR0.6995%CI0.47-1.01P=0.055Overall:HR0.9295%CI0.70-1.21P=0.545Time(y)Proportionhavinganevent(%)403020100012PerindoprilTime(y)42442637435618418670690123PerindoprilPlacebo1yr=HR0.6395%CI0.41-0.97P=0.033Overall:HR0.85995%CI0.614-1.202P=0.375Time(y)403020100Proportionhavinganevent(%)Time(y)48VALIDD

ValsartanInDiastolicDysfunction:EffectoftheAngiotensinIIAntagonistValsartanon

DiastolicFunctioninPatientswithHypertensionandDiastolicDysfunctionScottD.Solomon,RajeshJanardhanan,AnilVerma,MikhailBourgoun,YvesLaCourcier,StephenHippler,WilliamA.Kaye,HaroldFields,TasneemZ.Naqvi,WilliamL.Daley,SusanRitter,SharonMulvagh,J.MalcolmO.Arnold,MichaelZile,JamesD.Thomas,GerardP.AurigemmafortheVALIDDStudyInvestigatorsStudyDesignMenandWomen>45yrsoldHistoryoforNewlyDiagnosedHypertensionPreservedEjectionFraction(>50%)EvidenceofDiastolicDysfunction:(byDTI:age45-55,E’<10cm/s;age55-65,E’<9cm/s;age65+E’<8cm/s)Valsartan

320mgqd(plusStandardAntihypertensiveTherapy)n=186Non-RAAS(plusStandardAntihypertensiveTherapy)n=198PrimaryEndpoint:ChangeinDiastolicMyocardialrelaxationvelocity(E’),baselineto9monthsSecondaryEndpoints:IVRT,S’,DT,LVMassBloodPressureTreatedtoatargetof135/80inbotharmsutilizingamenuofconcomitantmedications(diuretics,betaorcalcium-channelblockers,alphablockers)excludingRAASinhibitors

RandomizationMulti-center,randomized,placebocontrolled,double-blindtrialn=384n=48238WeeksofRx50ChangeinMitralAnnularRelaxationVelocity(E’)FromBaselinetoFollow-UpBaseline9MonthsBaseline9Months7.98.08.48.5ValsartanAnnularRelaxationVelocity(E')(cm/s)Non-RAASP<0.0001P<0.00010.60(95%CI0.39,0.81)0.44(95%CI0.23,0.65)BetweenGroupsp=0.3051RelationshipBetweenBPLoweringAndImprovementinDiastolicFunction*p=0.01adjustingforbaselineBP,BaselineE’,ageandtreatmentgroup

52■I-PRESERVE

厄貝沙坦vs.安慰劑4128例,>60歲，EF>45%■TO