正常射血分数心力衰竭HFPEF诊断和治疗进展.ppt

正常射血分数心力衰竭(HF-PEF)诊断和治疗进展解放军总医院李小鹰,定义,左室收缩功能代偿性心衰(preservedleftventricularejectionfraction,PLVEF）左心室射血分数正常心力衰竭(heartfailurewithpreservedejectionfraction，HF-PEF）包括：（1）舒张性心力衰竭、（2）急性二尖瓣返流、主动脉瓣返流、（3）其他原因的循环充血状态。,有充血性心力衰竭典型的表现（肺循环和体循环淤血）非心脏瓣膜病静息时伴异常的舒张性功能不全收缩功能正常或仅有轻微减低,舒张性心力衰竭（diastolicheartfailure,DHF）,由于这些患者通常表现为典型的心力衰竭症状，因此应当将其归类到C期。孤立的舒张功能不全少见，通常伴有不同程度的收缩功能不全。,舒张性心力衰竭的病因与病理生理特点,HF-PEF的主要病因和诱发因素,老年人，女性心房颤动高血压伴左心室肥厚肺部感染糖尿病肾功能不全冠心病心肌缺血贫血肥胖限制性和浸润性心肌病,HF-PEF患者有高血压的比例,大多数HF-PEF患者有高血压大多数既往或目前有LVH,1.SenniMetal.Circulation.2019;98:2282-2289.4.OwanTEetal.NEnglJMed.2019;355:251-2592.VasanRSetal.JAmCollCard.2019;33:1948-1955.5.BhatiaRSetal.NEnglJMed.2019;355:260-2693.GottdienerJSetal.AnnInternMed.2019;137:631-639,Framingham2,Olmsted1,CHS3,Owan4,Bhatia5,37,36,170,60,59,78,880,1570,2167,2429,n=,患者(%),n=CHF患者总人数,55,63,59,75,58,49,48,57,71,50,0,20,40,60,80,100,EF尚正常,EF降低,从危险因素到心力衰竭,吸烟高脂血症糖尿病高血压,心梗,左室肥厚,收缩功能不良,舒张功能不良,心力衰竭(收缩性与舒张性）,左室结构和功能正常,左室重构,无症状左室功能不良,症状性心力衰竭,年,年/月,Levyetal.JAMA,275:1557,2019,Normal,SystolicHeartFailure,DiastolicHeartFailure,Aurigemma,Zile,GaaschCirculation2019,HF-PEF的发病机制和主要病理生理环节左心室向心性重构,左心室舒张功能障碍血管-心室硬度增大，扩张储备功能降低左心室长轴收缩功能减退对运动的心率变时效应减弱RAS和交感神经系统激活,HF-PEF患者主动脉可扩张性降低,HundleyWG,etal.JAmCollCardiol.2019;38:796-802.,PicogramsperMililiter,Controls,SHF,DHF,Controls,SHF,DHF,Controls,SHF,DHF,Norepinephrine,BrainNatriureticPeptide,C-TerminalAtrialNatriureticPeptide,Kitzman,etal.JAMA.2019;288:2144-2150.,神经内分泌功能: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,左心室功能不全的压力/容积机制,左心室压力,左心室容积,舒张功能不全高血压高龄左心室肥厚向心性重构,收缩功能不全心梗、心肌病、容量负荷过重高血压离心性重构,ZileMR,BrutsaertDL.Circulation.2019;105;1387-1393.,左心室舒张功能不全的进程,高血压老龄动脉粥样硬化糖尿病,血管肥厚弹力蛋白和胶原改变钙化内皮功能不全顺应性丧失,心肌肥厚纤维化/胶原改变凋亡心梗/缺血细胞功能不全顺应性丧失，舒张受损,心力衰竭,死亡、心梗、急性冠脉综合征、心衰、心律失常、卒中,1.ZileMR,BrutsaertDL.Circulation.2019;105;1503-1508;2.KassDA,etal.CirculationRes.2019;94:1533-1542.,舒张性心功能不全发病率及预后,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,年龄段,平均年龄,美国(CHS),芬兰(Helsinki),英国(Poole),丹麦.(Copen.),西班牙(Asturias),葡萄牙(EPICA),荷兰(Rotter.),瑞典(Vasteras),左心室收缩功能降低的比例,HF-PSF的比例,55,51,68,46,71,59,39,71,PetrieM,McMurrayJ.Lancet.2019;358:423-434.HoggKetal.JAmCollCard.2019;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.2019;98:2282-2289.2.VasanRSetal.JAmCollCard.2019;33:1948-1955.3.GottdienerJSetal.AnnInternMed.2019;137:631-639.,EF50%,EF50%,Owan5(n=4,596),Bhatia6(n=2,802),Patients(%),4.MasoudiFAetal.JAmCollCard.2019;41-217-223.5.OwanTEetal.NEnglJMed.2019;355:251-259.6.BhatiaRSetal.NEnglJMed.2019;355:260-269.,HF-PEF患病趋势,OwanTEetal.NEnglJMed.2019;355:251-259.,HF-PEF的死亡率,OwanTEetal.NEnglJMed.2019;355:251-259;BhatiaRSetal.NEnglJMed.2019;355:260-269.,1yearmortality,29,32,22.2,25.5,SHF与HF-PEF的预后(5年生存率)OWANTEetal.NEnglJMed2019;355:251-259,射血分数正常的患者,射血分数降低的患者,危险病例数,危险病例数,年,年,生存率,生存率,心力衰竭患者的再住院率,HoggKetal.JAmCollCard.2019;43:317-327.,诊断要点,+,+,收缩性HF(SHF)与HF-PEF:症状与体征,GivertzMMetal.In:BraunwaldE,ZipesDP,LibbyP,eds.HeartDisease,7thedition.Philadelphia,Pa:WBSaunders.2019;534-561.,ESC2019年建议舒张性心功能不全需同时满足以下的三个必要条件充血性心力衰竭的症状和体征。左室收缩功能正常或仅有轻度异常。左室松弛、充盈、舒张期扩张能力异常或舒张期僵硬的证据。,美国心脏病学会和美国心脏病协会（AHA/ACC）建议的诊断标准：,有典型的心力衰竭症状和体征，同时超声心动图显示患者左心室射血分数正常并且没有瓣膜疾病（如主动脉狭窄或二尖瓣返流）。AHH/ACC2019年慢性心力衰竭诊治指南,中国舒张性心力衰竭诊断标准（2019指南）,有典型心衰的症状和体征；LVEF正常（45%），左心腔大小正常；UCG有左室舒张功能异常的证据；UCG检查无瓣膜病，心包疾病及肥厚或限制型心肌病。,舒张性心力衰竭的诊断标准,YturraldeRFandGaaschWH.ProgCardiovascDis2019;47:314-319.KorensteinDetal.BMCEmergMed2019;7:6,HF-PEF诊断步骤(ESC共识,2019),HF的症状或体征,LVEF50%且左心室舒张末期容积指数(LVEDVI)12mmHg或左心室舒张末压16mmHg,组织多普勒,NTproBNP220pg/mlBNP200pg/ml,E/E15,15E/E8,超声血流多普勒:.E/ADT.肺静脉血流.左房扩大.左心室肥厚.房颤,NTproBNP220pg/mlorBNP200pg/ml,HFNEF,组织多普勒E/E8,FromPaulus.EurHeartJ.2019,辅助检查,超声心动图射血分数：45%舒张功能不全。二尖瓣血流频谱:E/AIVRT(等容舒张时间)EDT(E峰减速时间),三种异常的左室充盈模式：松弛受损型：轻度舒张功能异常，E峰下降A峰增高，EA减小。假性正常化充盈：中度舒张功能异常。EA和减速时间正常。限制型充盈模式：重度舒张功能异常E峰升高及减速时间缩短，EA显著增大。,左心室舒张功能超声心动图分析,HoCYetal.Circulation.2019;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危险)控制血压(证据水平:A)控制房颤患者的心室率(C)利尿剂控制肺淤血或外周水肿(C)IIa级(益处危险)冠心病患者冠脉再通术对舒张功能的效应(C)IIb级(益处危险)房颤患者转复为窦律(C)使用阻滞剂、ACEI、ARB或CCB良好控制血压以减轻心衰症状(C)地高辛减轻心衰症状(C),Huntetal.JAmCollCardiol.2019:46;e1-e82.,HF-PEF治疗推荐HeartFailureSocietyofAmericaPracticeGuideline(2019),低钠饮食C容量过度负荷患者使用噻嗪类或襻利尿剂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使用阻滞剂心肌梗死史A高血压B需要控制心室率的心房颤动B使用CCBdiltilzem或verapamil用于阻滞剂不能耐受的心房颤动C心绞痛症状A高血压C,AdamsKF,etal.JCardFail2019;12:10-38,CHARM-added,CHARM-preserved,CHARM研究,坎地沙坦在症状性心衰患者的研究,CHARM-alternative,n=2028LVEF18岁的症状性心力衰竭患者3023例(NYHA分级IIIV),左心室射血分数40%随访和主要终点主要终点:心血管死亡或因心力衰竭住院.平均随访36.6月治疗安慰剂或坎地沙坦,剂量逐渐增加到32mg,每天一次,YusufSetal.Lancet2019;362:777-781.,CHARM研究,NumberatRisk,NumberatRisk,Candesartan,Placebo,Candesartan,Placebo,CHARM-PreservedPrimaryoutcome:CVdeathorCHFhospitalisation,YusufSetal.Lancet.2019;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.Lancet2019;362:777-781.,PEP-CHF:培哚普利治疗老年人心力衰竭,入选标准:年龄70岁最近6个月内因心衰住院临床诊断HF利尿剂治疗舒张功能不全的证据随机:,培哚普利2mg,安慰剂,n=426,n=424,平均随访2.2年主要研究终点:全因死亡或心力衰竭住院,ClelandJG.EurHeartJ.2019;27:2338-2345.,HFhospitalization,Cleland,etal.EurHeartJ.2019;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=384,