正常射血分?jǐn)?shù)心力衰竭(HFPEF)診斷和治療進(jìn)展

1、正常射血分?jǐn)?shù)心力衰竭(HF-PEF)診斷和治療進(jìn)展1正常射血分?jǐn)?shù)心力衰竭(HFPEF)診斷和治療進(jìn)展定 義2正常射血分?jǐn)?shù)心力衰竭(HFPEF)診斷和治療進(jìn)展 左室收縮功能代償性心衰 (preserved left ventricular ejection fraction, PLVEF） 左心室射血分?jǐn)?shù)正常心力衰竭(heart failure with preserved ejection fraction，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正常射血分?jǐn)?shù)心力衰竭(HFPEF)診斷和治療進(jìn)展 有充血性心力衰竭典型的表現(xiàn)（

2、肺循環(huán)和體循環(huán)淤血） 非心臟瓣膜病 靜息時伴異常的舒張性功能不全 收縮功能正常或僅有輕微減低舒張性心力衰竭（diastolic heart failure, DHF）4正常射血分?jǐn)?shù)心力衰竭(HFPEF)診斷和治療進(jìn)展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正常射血分?jǐn)?shù)心力衰竭(HFPEF)診斷和治療進(jìn)展舒張性心力衰竭的病因與病理生理特點6正常射血分?jǐn)?shù)心力衰竭(HFPEF)診斷和治療進(jìn)展HF-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

3、血 肥胖 限制性和浸潤性心肌病7正常射血分?jǐn)?shù)心力衰竭(HFPEF)診斷和治療進(jìn)展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LVH1. Senni M et al. Circulation. 1998;98:2282-2289. 4. Owan TE et al. N Engl J Med. 2006;355:251-2592. Vasan RS et al. J Am Coll Card. 1999;33:1948-1955. 5. Bhatia RS et al. N Engl J Med. 2006;355:260-2693. Gottdiener JS

4、 et al. Ann Intern Med. 2002;137:631-639Framingham2Olmsted1CHS3Owan4Bhatia53736170605978880157021672429n=患者 (%)n =CHF患者總?cè)藬?shù)55635975584948577150020406080100EF尚正常EF降低8正常射血分?jǐn)?shù)心力衰竭(HFPEF)診斷和治療進(jìn)展 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 Levy et al. JAMA, 275:15

5、57, 19969正常射血分?jǐn)?shù)心力衰竭(HFPEF)診斷和治療進(jìn)展NormalSystolicHeart FailureDiastolicHeart FailureAurigemma, Zile, GaaschCirculation 200510正常射血分?jǐn)?shù)心力衰竭(HFPEF)診斷和治療進(jìn)展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)張儲備功能降低 左心室長軸收縮功能減退 對運動的心率變時效應(yīng)減弱 RAS和交感神經(jīng)系統(tǒng)激活 11正常射血分?jǐn)?shù)心力衰竭(HFPEF)診斷和治療進(jìn)展HF-PEF患者主動脈可擴(kuò)張性降低Hundley WG, et

6、 al. J Am Coll Cardiol. 2001;38:796-802. Distensibility (10-3 mm Hg)12正常射血分?jǐn)?shù)心力衰竭(HFPEF)診斷和治療進(jìn)展Picograms per MililiterControlsSHFDHFControlsSHFDHFControlsSHFDHFNorepinephrineBrain Natriuretic PeptideC-Terminal Atrial Natriuretic PeptideKitzman, et al. JAMA. 2002; 288:2144-2150.神經(jīng)內(nèi)分泌功能: SHF, isolated

7、DHF and controls25002000150010005000900800500400100070060020030050045030025050040035010020015013正常射血分?jǐn)?shù)心力衰竭(HFPEF)診斷和治療進(jìn)展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)Zile MR, Brutsaert DL. Circulation. 2002;105;1387-1393.14正常射血分?jǐn)?shù)心力衰竭(HFPEF)診斷和治療進(jìn)展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

8、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. Zile MR, Brutsaert DL. Circulation. 2002;105;1503-1508; 2. Kass DA, et al. Circulation Res. 2004;94:1533-1542.15正常射血分?jǐn)?shù)心力衰竭(HFPEF)診斷和治療進(jìn)展舒張性心功能不全發(fā)病率及預(yù)后16正常射血分?jǐn)?shù)心力衰竭(HFPEF)診斷和治療進(jìn)展心力衰竭患病率66-10375-8670-84755040

9、2555-95787675606865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5551684671593971Petrie M, McMurray J. Lancet. 2001;358:423-434. Hogg K et al. J Am Coll Card. 2004;43:317-327.CHF患病率 (%)01234567891017正常射血分?jǐn)?shù)心力衰竭(HFPEF)診斷和治療進(jìn)展心力衰竭患者

10、中HF-PEF的比例EF50%EF45%EF50%EF50%Framingham2(n=73)Olmstead1(n=137)CHS3 (n=269)NHF Project4(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. EF50%EF 50%Owan5(n=4,596)Bhatia6(n=2,802)

11、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;355:260-269.18正常射血分?jǐn)?shù)心力衰竭(HFPEF)診斷和治療進(jìn)展19正常射血分?jǐn)?shù)心力衰竭(HFPEF)診斷和治療進(jìn)展HF-PEF患病趨勢 Owan TE et al. N Engl J Med. 2006;355:251-259.20正常射血分?jǐn)?shù)心力衰竭(HFPEF)診斷和治療

12、進(jìn)展HF-PEF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 mortality293222.225.521正常射血分?jǐn)?shù)心力衰竭(HFPEF)診斷和治療進(jìn)展SHF與HF-PEF的預(yù)后(5年生存率)OWAN TE et al. N Engl J Med 2006; 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正常射血分?jǐn)?shù)心力衰竭(HFPEF)診斷和治療進(jìn)展心力衰竭患

13、者的再住院率 Hogg K et al. J Am Coll Card. 2004;43:317-327.Readmission rates (%)Philbin et alMalki et alSmith et alDauterman et alHeart failure with preserved systolic function(HF-PEF)44264658Systolic heart failure(SHF)4233465823正常射血分?jǐn)?shù)心力衰竭(HFPEF)診斷和治療進(jìn)展診 斷 要 點24正常射血分?jǐn)?shù)心力衰竭(HFPEF)診斷和治療進(jìn)展參數(shù)SHFHF-PSF病史冠心病高血壓糖

14、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Givertz MM et al. In: Braunwald E, Zipes DP, Libby P, eds. Heart Disease, 7th edition. Philadelphia,

15、 Pa: WB Saunders. 2001;534-561.25正常射血分?jǐn)?shù)心力衰竭(HFPEF)診斷和治療進(jìn)展 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)張能力異常或舒張期僵硬的證據(jù)。26正常射血分?jǐn)?shù)心力衰竭(HFPEF)診斷和治療進(jìn)展美國心臟病學(xué)會和美國心臟病協(xié)會（AHA/ACC）建議的診斷標(biāo)準(zhǔn)： 有典型的心力衰竭癥狀和體征，同時超聲心動圖顯示患者左心室射血分?jǐn)?shù)正常并且沒有瓣膜疾?。ㄈ缰鲃用}狹窄或二尖瓣返流）。 AHH/ACC 2005年慢性心力衰竭診治指南 27正常射血分?jǐn)?shù)心力

16、衰竭(HFPEF)診斷和治療進(jìn)展中國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檢查無瓣膜病，心包疾病及肥厚或限制型心肌病。28正常射血分?jǐn)?shù)心力衰竭(HFPEF)診斷和治療進(jìn)展舒張性心力衰竭的診斷標(biāo)準(zhǔn) Yturralde RF and Gaasch WH. Prog Cardiovasc Dis 2005;47:314-319. Korenstein D et al. BMC Emerg Med 2007;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)

17、準(zhǔn) (5-7分:可能HF; 8-12分: 確診HF)血漿BNP升高 (400 pg/ml3) 或胸部X-線示肺淤血心肺運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)29正常射血分?jǐn)?shù)心力衰竭(HFPEF)診斷和治療進(jìn)展HF-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)(LVED VI) 12 mmHg或左心室舒張末壓16 mmHg組織多普勒NT proBNP 220 pg/mlBNP 200

18、pg/mlE/E 1515 E/E 8超聲血流多普勒 :. E/A DT. 肺靜脈血流. 左房擴(kuò)大 . 左心室肥厚. 房顫NT proBNP 220 pg/mlor BNP 200 pg/mlHFNEF組織多普勒E / E 8 From Paulus. Eur Heart J. 200730正常射血分?jǐn)?shù)心力衰竭(HFPEF)診斷和治療進(jìn)展輔 助 檢 查31正常射血分?jǐn)?shù)心力衰竭(HFPEF)診斷和治療進(jìn)展 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正常射血分?jǐn)?shù)心力衰竭(HFPEF)診斷和治療進(jìn)展三種異常的左室充盈模

19、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峰升高及減速時間縮短， EA顯 著增大。 33正常射血分?jǐn)?shù)心力衰竭(HFPEF)診斷和治療進(jìn)展左心室舒張功能超聲心動圖分析Ho CY et al. Circulation. 2006;113:e396-398e. 34正常射血分?jǐn)?shù)心力衰竭(HFPEF)診斷和治療進(jìn)展The Hong Kong Diastolic Heart Failure Study Normal DHF p-value Number 38 151 Female/Mal

20、e 24 / 14 93 / 58 Age (years) 72 7 74 7 0.11 IVSd (cm) 1.2 0.2 1.4 0.3 0.001 LVEDD (cm) 4.4 0.5 4.9 0.7 0.001 LVESD (cm) 2.9 0.5 3.4 0.7 0.068 FS (%) 36 6 32 8 0. 0.005 LVEF2d (%) 62 8 67 10 0.12 LVmass (g) 211 61 305 94 0.001 LAD (cm) 3.4 0.4 4.1 0.7 0.001 E (m/s) 0.67 0.2 0.65 0.2 0.52 A (m/s) 0.7

21、9 0.2 0.92 0.2 0.0005 E/A 0.9 0.3 0.7 0.3 0.0005 DT (ms) 200 63 259 77 0.0005 IVRT (ms) 100 18 117 32 0.0005 E/Em 12 3 20 9 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)Hunt et al. J Am Co

22、ll Cardiol. 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、病例研究或臨床實踐的共識40正常射血分?jǐn)?shù)心力衰竭(HFPEF)診斷和治療進(jìn)展HF-PEF治療推薦Heart Failure Society of America Practice Guideline (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 使用阻滯劑 心肌梗死史 A 高血壓 B 需要控制心

23、室率的心房顫動 B 使用CCB diltilzem或verapamil用于阻滯劑不能耐受的心房顫動 C 心絞痛癥狀 A 高血壓 CAdams KF, et al. J Card Fail 2006;12:10-3841正常射血分?jǐn)?shù)心力衰竭(HFPEF)診斷和治療進(jìn)展CHARM-addedCHARM-preserved CHARM 研究坎地沙坦在癥狀性心衰患者的研究CHARM-alternative n=2028 LVEF 40%不能耐受ACEIn=2548LVEF 40%使用或不使用ACEIPrimary outcome for overall program: All-cause death

24、Primary outcome for each trial: CV death or HF hospitalizationHF, heart failure; LVEF, left ventricular ejection fraction.Pfeffer MA et al. Lancet. 2003;362:759-766.單獨使用ARBACEI+ARB有或無ACEI+ARB42正常射血分?jǐn)?shù)心力衰竭(HFPEF)診斷和治療進(jìn)展CHARM-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

25、力衰竭患者3023例 (NYHA分級 IIIV), 左心室射血分?jǐn)?shù)40%隨訪和主要終點主要終點: 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32 mg ,每天一次Yusuf S et al. Lancet 2003;362:777-781.43正常射血分?jǐn)?shù)心力衰竭(HFPEF)診斷和治療進(jìn)展CHARM 研究Number at RiskNumber at RiskCandesartanPlaceboCandesartanPlacebo單獨使用ARB組101310158317984344271221269298871013101583179843442

26、7122126929887504000233.5Time (Years)3020101504000233.5Time (Years)3020101PlaceboCandesartanProportion with CV Death oror Hospitalization for CHF23% RR, p = 0.0004ACEI+ARB組12761272106310139489064574221176113612761272106310139489064574221176113650400Time (Years)302010233.510233.51PlaceboCandesartanPro

27、portion with CV Death oror Hospitalization for CHF15% RR, p = 0.01左室舒張功能不全組1514150913771359833824182195145814411514150913771359833824182195145814410233.5Time (Years)10233.5Time (Years)1PlaceboCandesartanProportion with CV Death oror Hospitalization for CHF11% RR, p = 0.12504003020105040030201044正常射血

28、分?jǐn)?shù)心力衰竭(HFPEF)診斷和治療進(jìn)展CHARM-Preserved Primary outcome: CV death or CHF hospitalisation0123years3.50102030PlaceboCandesartan51525HR 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 riskCandesartan 1514 1458 1377 833 182Pla

29、cebo 1509 1441 1359 824 19545正常射血分?jǐn)?shù)心力衰竭(HFPEF)診斷和治療進(jìn)展CV death, CHF hosp.333 366 - CV death170170 -CHF hosp. 241276CV death, HF hosp,365399 MI CV death, HF hosp,388429 MI, stroke CV death, HF hosp,460497 MI, stroke, revasc candesartan betterHazard ratioplacebo better0.81.01.2p-value0.9180.0720.1180.1

30、260.0780.123Covariateadjustedp-value0.6350.0470.0510.0510.0370.13CandesartanPlacebo0.890.990.850.900.880.91CHARM-Preserved Primary and secondary outcomesYusuf S et al. Lancet 2003;362:777-781.46正常射血分?jǐn)?shù)心力衰竭(HFPEF)診斷和治療進(jìn)展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=

31、424 平均隨訪 2.2年 主要研究終點:全因死亡或心力衰竭住院Cleland JG. Eur Heart J. 2006;27:2338-2345.47正常射血分?jǐn)?shù)心力衰竭(HFPEF)診斷和治療進(jìn)展HF hospitalization Cleland, et al. Eur Heart J. 2006; 27:2338-2345. Death and HF hospitalization37069Placebo3PEP-CHF: Effect of perindopril in HF-PEF patientsPt. at riskPerindoprilPlacebo012424426374

32、356184186Perindopril1 yr =HR 0.6995% CI 0.47-1.01P=0.055Overall:HR 0.9295% CI 0.70-1.21 P=0.545Time (y)Proportion having an event (%)403020100012PerindoprilTime (y)42442637435618418670690123PerindoprilPlacebo1 yr =HR 0.6395% CI 0.41-0.97P=0.033Overall:HR 0.85995% CI 0.614-1.202P=0.375Time (y)4030201

33、00Proportion having an event (%)Time (y)48正常射血分?jǐn)?shù)心力衰竭(HFPEF)診斷和治療進(jìn)展VALIDD Valsartan In Diastolic Dysfunction: Effect of the Angiotensin II Antagonist Valsartan on Diastolic Function in Patients with Hypertension and Diastolic DysfunctionScott D. Solomon, Rajesh Janardhanan, Anil Verma, Mikhail Bourgo

34、un,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 Investigators49正常射血分?jǐn)?shù)心力衰竭(HFPEF)診斷和治療進(jìn)展Study DesignMen and Women 45 yrs o

35、ldHistory of or Newly Diagnosed HypertensionPreserved 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 = 186Non- RAAS(plus Standard Antihypertensive Therapy)n = 19

36、8Primary Endpoint: Change in Diastolic Myocardial relaxation velocity (E), baseline to 9 monthsSecondary Endpoints: IVRT, S, DT, LV MassBlood 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)

37、excluding RAAS inhibitors RandomizationMulti-center, randomized, placebo controlled, double-blind trialn = 384n = 48238 Weeks of Rx50正常射血分?jǐn)?shù)心力衰竭(HFPEF)診斷和治療進(jìn)展Change in Mitral Annular Relaxation Velocity (E) From Baseline to Follow-UpBaseline9 MonthsBaseline9 Months7.37.47.57.67.77.87.98.08.18.28.38.48.5ValsartanAnnular Relaxation Velocity (E) (cm/s)Non-RAASP 0.0001P 60 歲，EF 45 % TOP CAT 安體舒通 vs. 安慰劑 4500 例, 6