正常射血分数心力衰竭(HF-PEF)诊断和治疗进展课件.ppt

*,Click to edit Master title style,*,Click to edit Master text styles,Second level,Third level,Fourth level,Fifth level,Click to edit Master title style,Click to edit Master text styles,Second level,Third level,Fourth level,Fifth level,Click to edit Master title style,Click to edit Master text styles,Second level,Third level,Fourth level,Fifth level,Click to edit Master title style,Click to edit Master text styles,Second level,Third level,Fourth level,Fifth level,定 义,1,左室收缩功能代偿性心衰,(preserved left ventricular ejection fraction,PLVEF,）,左心室射血分数正常心力衰竭,(heart failure with preserved ejection fraction,，,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。,2,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,（,diastolic heart failure,DHF,）,3,NYHA,心功能分级,分级,患者自觉的活动能力及症状,I,级,有心脏病，无明显活动受限,II,级,一般体力活动出现心力衰竭症状,III,级,轻微活动即出现心力衰竭症状,IV,级,静息时仍有心力衰竭症状,这种分级方案优点是简便易行，缺点是仅凭患者的主观陈述，有时症状与客观检查有很大差距，同时患者个体之间的差异也较大。此外，各分级之间的治疗方案无明显差异,Hunt SA,et al.J Am Coll Cardiol 2005;46(6):e1-82.,叶任高等主编,.,内科学（第,6,版）,6,NYHA,心功能分级,ACC/AHA,心衰分期,A,期,有心衰危险但无结构性心脏疾病和心衰症状,I,级,有心脏病，无明显活动受限,B,期,有结构性心脏疾病但无心衰症状,II,级,一般体力活动出现心衰症状,C,期,有结构性心脏疾病并既往或当前有心衰症状,III,级,轻微活动即出现心衰症状,IV,级,静息时仍有心衰症状,D,期,顽固性心衰需特殊治疗,ACC/AHA,心衰诊治指南心衰分期与,NYHA,心功能分级的区别,Shocken DD,et al.,Circulation,2008;117:000-000,JAMA 2002;287(7):890-897,7,早期干预，最终获益,心力衰竭事件链的治疗,重点在于预防,Dzau V,et al.Am Heart J 1991;121:1244-63.,Hunt SA,et al.J Am Coll Cardiol 2005;46(6):e1-82.,8,舒张性心力衰竭的病因与病理生理特点,9,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,10,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.,Senni M,et al,.,Circulation,.1998;98:2282-2289,.,4.,Owan TE,et al,.,N Engl J Med,.2006;355:251-259,2.,Vasan RS,et al,.,J Am Coll Card,.1999;33:1948-1955.,5.Bhatia RS,et al,.,N Engl J Med,.2006;355:260-269,3.,Gottdiener JS,et al,.,Ann Intern Med,.2002;137:631-639,Framingham,2,Olmsted,1,CHS,3,Owan,4,Bhatia,5,37,36,170,60,59,78,880,1570,2167,2429,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,11,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,Levy et al.JAMA,275:1557,1996,12,Normal,Systolic,Heart Failure,Diastolic,Heart Failure,Aurigemma,Zile,Gaasch,Circulation 2005,13,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,14,HF-PEF,患者主动脉可扩张性降低,Hundley WG,et al.,J Am Coll Cardiol.,2001;38:796-802.,Distensibility(10,-3,mm Hg),15,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,Zile MR,Brutsaert DL.,Circulation,.2002;105;1387-1393.,16,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.Zile MR,Brutsaert DL.,Circulation,.2002;105;1503-1508;,2.Kass DA,et al,.,Circulation Res,.2004;94:1533-1542.,17,舒张性心功能不全发病率及预后,18,心力衰竭患者中,HF-PEF,的比例,EF,50%,EF,45%,EF,50%,EF,50%,Framingham,2,(n=73),Olmstead,1,(n=137),CHS,3,(n=269),NHF Project,4,(n=19,710),1.Senni M,et al,.,Circulation,.1998;98:2282-2289,.,2.,Vasan RS,et al,.,J Am Coll Card,.1999;33:1948-1955.,3.,Gottdiener JS,et al,.,Ann Intern Med,.2002;137:631-639.,EF,50%,EF,50%,Owan,5,(n=4,596),Bhatia,6,(n=2,802),Patients(%),4.,Masoudi FA,et al,.,J Am Coll Card,.2003;41-217-223.,5.,Owan TE,et al,.,N Engl J Med,.2006;355:251-259.,6.Bhatia RS,et al,.,N Engl J Med,.2006;355:260-269,.,19,20,HF-PEF,患病趋势,Owan TE,et al,.,N Engl J Med,.2006;355:251-259.,21,HF-P,E,F,的死亡率,Owan TE,et al,.,N Engl J Med,.2006;355:251-259;,Bhatia RS,et al,.,N Engl J Med,.2006;355:260-269.,1 year mortality,29,32,22.2,25.5,22,SHF,与,HF-PEF,的预后,(5,年生存率,),OWAN TE et al.N Engl J Med 2006;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,23,诊 断 要 点,24,ESC,2005,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。,25,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/ACC 2005,年慢性心力衰竭诊治指南,26,中国舒张性心力衰竭诊断标准（,2007,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,。,27,HF-PEF,诊断步骤,(,ESC,共识,2007),HF,的症状或体征,LVEF 50%,且 左心室舒张末期容积指数,(,LVED VI,),12 mmHg,或,左心室舒张末压,16 mmHg,组织多普勒,NT proBNP 220 pg/ml,BNP 200 pg/ml,E/E 15,15 E/E 8,超声血流多普勒,:,.E/A,DT,.,肺静脉血流,.,左房扩大,.,左心室肥厚,.,房颤,NT proBNP 220 pg/ml,or,BNP 200 pg/ml,HFNEF,组织,多普勒,E/E 8,From Paulus,.,Eur Heart J.2007,28,辅 助 检 查,29,超声心动图,射血分数,：,45%,舒张功能不全。,二尖瓣血流频谱,:E/A,IVRT(,等容舒张时间,),EDT(E,峰减速时间,),30,三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，,E,A,减小。,假性正常化充盈,：,中度舒张功能异常。,E,A,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，,E,A,显 著增大。,31,左心室舒张功能超声心动图分析,Ho CY,et al,.,Circulation,.2006;113:e396-398e,.,32,心电图,：,可发现心房颤动及其它心律失常；心肌梗死、缺血征象；左室肥厚征象,;PtfV1,负值增大。,血浆心房肽和脑钠肽,：高于正常血浆水平提示心力衰竭。,33,胸片,：,肺瘀血、肺水肿，心脏大小正常或心脏略扩大。,核医学检查、心导管与冠脉造影检查等,34,舒张性心力衰竭治疗原则,35,HF-PSF,治疗建议,(,ACC/AHA,2005),I,级,(,益处,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),Hunt,et al,.,J Am Coll Cardiol,.2005:46;e1-e82.,证据水平,A,资料来源于多中心、随机临床研究或荟萃分析结果,B,资料来源于单中心随机临床研究或非随机研究,C,仅仅是专家意见、病例研究或临床实践的共识,36,HF-PEF,治疗推荐,Heart Failure Society of America Practice Guideline(2006),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,ACEIs ARBs:B,ACEI:C,合并冠心病或糖尿病患者使用,ACEIs,或,ARBs C,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,CCB,diltilzem,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,Adams KF,et al.J Card Fail 2006;12:10-38,37,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=2028,LVEF 40%,不能耐受,ACEI,n=2548,LVEF 40%,使用或不使用,ACEI,Primary outcome for overall program:All-cause death,Primary outcome for each trial:CV death or HF hospitalization,HF,heart failure;LVEF,left ventricular ejection fraction.,Pfeffer MA et al.Lancet.2003;362:759-766.,单独使用,ARB,ACEI+ARB,有或无,ACEI+ARB,38,CHARM-Preserved,目的,验证,ARB,坎地沙坦能否使,左心室收缩功能尚存的,慢性心力衰竭,患者受益,设计,多国多中心、随机、双盲、,安慰剂,对照试验,患者,年龄,18,岁的症状性心力衰竭患者,3023,例,(NYHA,分级,II,IV),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,32 mg,每天一次,Yusuf S,et al,.,Lancet,2003;362:777-781.,39,CHARM,研究,Number at Risk,Number at Risk,Candesartan,Placebo,Candesartan,Placebo,单独使用,ARB,组,1013,1015,831,798,434,427,122,126,929,887,1013,1015,831,798,434,427,122,126,929,887,50,40,0,0,2,3,3.5,Time(Years),30,20,10,1,50,40,0,0,2,3,3.5,Time(Years),30,20,10,1,Placebo,Candesartan,Proportion with CV Death or,or Hospitalization for CHF,23%RR,p=0.0004,ACEI+ARB,组,1276,1272,1063,1013,948,906,457,422,1176,1136,1276,1272,1063,1013,948,906,457,422,1176,1136,50,40,0,Time(Years),30,20,10,2,3,3.5,1,0,2,3,3.5,1,Placebo,Candesartan,Proportion with CV Death or,or Hospitalization for CHF,15%RR,p=0.01,左室舒张,功能不全组,1514,1509,1377,1359,833,824,182,195,1458,1441,1514,1509,1377,1359,833,824,182,195,1458,1441,0,2,3,3.5,Time(Years),1,0,2,3,3.5,Time(Years),1,Placebo,Candesartan,Proportion with CV Death or,or Hospitalization for CHF,11%RR,p=0.12,50,40,0,30,20,10,50,40,0,30,20,10,40,CHARM-Preserved,Primary outcome,:,CV,death,or CHF hospitalisation,0,1,2,3,years,3.5,0,10,20,30,Placebo,Candesartan,5,15,25,HR 0.89(95%CI 0.77-1.03),p=0.118Adjusted HR 0.86,p=0.051,%,366(24.3%),333(22.0%),Yusuf S,et al,.,Lancet.,2003;362:777781.,Number at risk,Candesartan 1514,1458,1377,833 182,Placebo,1509,1441,1359,824,195,41,CV death,CHF hosp.,333,366,-CV death,170,170,-CHF hosp.,241,276,CV death,HF hosp,365,399,MI,CV death,HF hosp,388,429,MI,stroke,CV death,HF hosp,460,497,MI,stroke,revasc,candesartan better,Hazard ratio,placebo better,0.8,1,.0,1.2,p-value,0.918,0.072,0.118,0.126,0.078,0.123,Covariate,adjustedp-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-Preserved,Primary and secondary outcomes,Yusuf S,et al,.,Lancet,2003;362:777-781.,42,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,Cleland JG.,Eur Heart J,.2006;27:2338-2345.,43,HF hospitalization,Cleland,et al,.,Eur Heart J,.2006;27:2338-2345.,Death and,HF hospitalization,3,70,69,Placebo,3,PEP-CHF:Effect of perindopril in HF-PEF patients,Pt.at risk,Perindopril,Placebo,0,1,2,424,426,374,356,184,186,Perindopril,1 yr=,HR 0.69,95%,CI 0.47-1.01,P=0.055,Overall:,HR 0.92,95%CI 0.70-1.21,P=0.545,Time(y),Proportion having an event(%),40,30,20,10,0,0,1,2,Perindopril,Time(y),424,426,374,356,184,186,70,69,0,1,2,3,Perindopril,Placebo,1 yr=,HR 0.63,95%,CI 0.41-0.97,P=0.033,Overall:,HR 0.859,95%CI 0.614-1.202,P=0.375,Time(y),40,30,20,10,0,Proportion having an event(%),Time(y),44,VALIDD,Val,sartan,I,n,D,iastolic,D,ysfunction:Effect of the Angiotensin II Antagonist Valsartan on Diastolic Function in Patients with Hypertension and Diastolic Dysfunction,Scott D.Solomon,Rajesh Janardhanan,Anil Verma,Mikhail Bourgoun,Yves LaCourcier,Stephen Hippler,William A.Kaye,Harold Fields,Tasneem Z.Naqvi,William L.Daley,Susan Ritter,Sharon Mulvagh,J.Malcolm O.Arnold,Michael Zile,James D.Thomas,Gerard P.Aurigemma,for the VALIDD Study Investigators,Study Design,Men and Women 45 yrs old,History of or Newly Diagnosed Hypertension,Preserved Ejection Fraction(50%),Evidence of Diastolic Dysfunction:,(by DTI:age 45-55,E 10cm/s;age 55-65,E 9cm/s;age 65+E 8 cm/s),Valsartan,320 mg qd,(plus Standard Antihypertensive,Therapy),n=186,Non-RAAS,(plus Standard Antihypertensive,Therapy),n=198,Primary Endpoint:,Change in Diastolic Myocardial relaxation velocity(E),baseline to 9 months,Secondary Endpoints:,IVRT,S,DT,LV Mass,Blood Pressure Treated to a target of 135/80 in both arms utilizing a menu of concomitant medications(diuretics,beta or calcium-channel blockers,alpha blockers)excluding RAAS inhibitors,Randomization,Multi-center,randomized,placebo controlled,double-blind trial,n=384,n=482,38 Weeks of Rx,46,Change in Mitral Annular Relaxation Velocity(E)From Baseline to Follow-Up,Baseline,9 Months,Baseline,9 Months,7.3,7.4,7.5,7.6,7.7,7.8,7.9,8.0,8.1,8.2,8.3,8.4,8.5,Valsartan,Annular Relaxation Velocity(E)(cm/s),Non-RAAS,P 0.0001,P 60,岁，,EF 45%,HF-PEF,的重要临床试验,48,I-P,RESERVE:,患者基线特征,与流行病学和大样本临床资料比较,I-P,RESERVE,(n=4,1,33,),Cohort&Epi,Studies,Age(mean),72,75,Women,60%,65-70%,EF,59%,60%,1 cause of HF,Hypertension,6,4,%,60%,CAD,25%,25%,History of HTN,88%,80-90%,History of MI,2,4,%,20%,Prior CABG/PCI,13%,20%,Stroke/TIA,10%,na,Atrial fibrillation,29%,20-30%,Diabetes,27%,20-30%,McMurray JJV,et al.Euro J Heart Fail.2008;10:149,49,I-PRESERVE,:,治疗方案,*,Forced titration,2 weeks,PLACEBO,IRBESARTAN,75mg*,150mg,300mg,w2,w4,w8,M6,M10,M10,M24-48,Final visit,4 1,33,patients randomised May 2005;,completion April May 2008,Follow-up 2,-,4 years,w1,Inclusion,Titration,Maintenance,50,I-PRESERVE:,终点事件,主要终点:,全因死亡或,心血管,病原因住院,心血管病住院原因包括,:,心力衰竭加重,不稳定性心绞痛,心肌梗死,室性心律失常,房性心律失常,脑卒中,次要终点:,心血管病死亡、非致死性心肌梗死或非致死性脑卒中,心力衰竭死亡或心力衰竭住院,BNP,明尼苏达心力衰竭生活质量评分,(,LWHF,),51,I-PRESERVE,结果,（,/1000,人年）,IRBESARTAN,安慰剂,P,主要终点,100.4 105.4 0.35,总死亡率,52.6 52.3 0.44,CVD,住院率,70.6 74.3 0.44,52,I-PRESERVE,结论,厄贝沙坦不能改善心力衰竭而射血分数基本正常患者的预后。,53,摘 要,HF-PEF,患者多见于老年人和女性。,HF-PEF,与,EF,降低的心力衰竭比较,较多患者合并高血压或心房颤动,合并冠心病相对较少。,HF-PEF,与,EF,降低的心力衰竭比较,发生率增长明显，虽然死亡率相对较低，但住院率类似。,HF-PEF,的治疗益处尚缺乏肯定确切的循证证据。,54,谢谢！,55,