結(jié)締組織病相關(guān)肺動(dòng)脈高壓課件

1、結(jié)締組織病相關(guān)肺動(dòng)脈高壓什么是肺動(dòng)脈高壓？PEKING UNION MEDICAL COLLEGE HOSPITALPEKING UNION MEDICAL COLLEGE HOSPITALPAH肺動(dòng)脈高壓的發(fā)病機(jī)制PEKING UNION MEDICAL COLLEGE HOSPITAL肺動(dòng)脈高壓=肺循環(huán)疾病PEKING UNION MEDICAL COLLEGE HOSPITAL1. Pulmonary Arterial Hypertension Idiopathic PAH Heritable PAH Associated with:Connective tissue disease H

2、IV infectionPortal hypertensionSystematic to pulmonary shuntSchistosomiasisChronic hemolytic anemia Drugs and toxins induced PPHN 3. Pulmonary hypertension due to lung diseases and / or hypoxia COPD Interstitial lung disease Sleep-disordered breathing Other pulmonary diseases with mixed obstructive

3、and restrictive patterns Chronic exposure to high altitudeDevelopmental anomalities1 Pulmonary veno occlusive disease and pulmonary capillary hemangiomatosis 4. Chronic Thromboembolic Pulmonary Hypertension5. Pulmonary hypertension with unclear or multifactorial mechanismsUpdated diagnostic classifi

4、cation of PH(The 4th WHO - 2008, Dana Point) 2. Pulmonary hypertension due to left heart disease Systolic dysfunction Diastolic dysfunction Valvular diseasePEKING UNION MEDICAL COLLEGE HOSPITAL肺高壓的“歐姆定律”肺動(dòng)脈肺肌性小動(dòng)脈肺毛細(xì)血管床肺小靜脈肺靜脈左心房肺動(dòng)脈血栓和栓塞IPAH、FPAH、PPHN、CTD/HIV/門脈高壓etc.左向右分流PVODPCHPaO2I型：DPLD/高原病/肺泡毛細(xì)血

5、管發(fā)育不良II型：COPD/OSAS左房或左室心臟病瓣膜病UIRCTD肺靜脈受壓肺動(dòng)脈受壓PEKING UNION MEDICAL COLLEGE HOSPITALPH（肺循環(huán)高壓、肺動(dòng)脈高壓）：各種原因引起肺血管阻力進(jìn)行性增高為特征的臨床-病理生理綜合征。導(dǎo)致右心負(fù)荷增大，右心功能不全引起的系列臨床表現(xiàn)。PAH（動(dòng)脈型肺動(dòng)脈高壓、肺動(dòng)脈高壓）：病變直接累及肺動(dòng)脈并引起肺動(dòng)脈結(jié)構(gòu)和功能改變的肺動(dòng)脈高壓。 PEKING UNION MEDICAL COLLEGE HOSPITAL肺動(dòng)脈高壓定義PEKING UNION MEDICAL COLLEGE HOSPITAL結(jié)締組織病發(fā)生PAH的機(jī)制孤立

6、的肺血管病變肺小血管炎肺小動(dòng)脈血栓栓塞肺小血管收縮、舒張因子失衡肺血管痙攣（雷諾現(xiàn)象）繼發(fā)于肺間質(zhì)纖維化繼發(fā)于心臟病變血栓栓塞肺間質(zhì)纖維化PEKING UNION MEDICAL COLLEGE HOSPITALCTDPAH是一種常見的臨床病理生理綜合征PEKING UNION MEDICAL COLLEGE HOSPITALCTD是相關(guān)因素所致PAH的首要原因法國(guó)PAH注冊(cè)登記研究PEKING UNION MEDICAL COLLEGE HOSPITALCTD是相關(guān)因素所致PAH的首要原因美國(guó)REVEAL注冊(cè)研究Badesch DB, et al. Chest. 2010;137:376PE

7、KING UNION MEDICAL COLLEGE HOSPITALCTD是相關(guān)因素所致PAH的首要原因中國(guó)的注冊(cè)研究PEKING UNION MEDICAL COLLEGE HOSPITALPAH是CTD不容忽視的合并癥2.6%（日本，Yoshida S，2001）8% （USA，NIH，1987）3.7%（中國(guó)，北京協(xié)和醫(yī)院，2006，82/2189）4.2%（中國(guó)，廣東省人民醫(yī)院，2009,79/1892）3.89% in SLE（中國(guó)，CSTAR，2011，77/1980）PEKING UNION MEDICAL COLLEGE HOSPITALPAH是CTD不容忽視的合并癥PEKI

8、NG UNION MEDICAL COLLEGE HOSPITAL肺動(dòng)脈高壓（PAH）北京協(xié)和醫(yī)院結(jié)締組織病住院患者統(tǒng)計(jì)PAH是CTD不容忽視的合并癥PEKING UNION MEDICAL COLLEGE HOSPITALCTDPAH構(gòu)成的地域差異PEKING UNION MEDICAL COLLEGE HOSPITAL北京協(xié)和醫(yī)院中華風(fēng)濕病學(xué)雜志 1999 第1期中華內(nèi)科雜志. 2006 Jun;45(6):467-71不同CTD中PAH的患病率廣東省人民醫(yī)院PEKING UNION MEDICAL COLLEGE HOSPITALPAH是CTD不容忽視的合并癥中國(guó)患病率居世界各種族第二位

9、92.9/100,000估計(jì)中國(guó)狼瘡患者1,000,000PEKING UNION MEDICAL COLLEGE HOSPITALSLEPM/DMSSSec APSPri APSAPSSScMCTDn = 1133n = 270n = 421n = 38n = 8n = 46n = 5n = 34n = 19n = 3n = 70n = 31n = 1n = 4n = 10n = 14PHNo PH系統(tǒng)性紅斑狼瘡（SLE）的患病數(shù)具于首位PAH是CTD不容忽視的合并癥PAH是嚴(yán)重影響CTD患者預(yù)后的危險(xiǎn)因素PEKING UNION MEDICAL COLLEGE HOSPITALI類PAH

10、中不同原因的預(yù)后YearsCHDIPAHMcLaughlin VV, et al. Chest, 2004;126:78PEKING UNION MEDICAL COLLEGE HOSPITALCTD-PAH vs.IPAH：美國(guó)REVEAL研究Chung L, et al. Chest, 2010;138:13831年生存率和無(wú)住院率：IPAHCTD-PAHPEKING UNION MEDICAL COLLEGE HOSPITALCTD-PAH vs.IPAH：中國(guó)注冊(cè)PEKING UNION MEDICAL COLLEGE HOSPITALPAH已成為SSc患者的主要死因中位生存時(shí)間1年1

11、年存活率為55%2年40-55%5年10%（不伴PAH的SSc為80%）PEKING UNION MEDICAL COLLEGE HOSPITALSSc-PAH vs.IPAHPEKING UNION MEDICAL COLLEGE HOSPITALProgress Cardio Dis, 2002; 45:225SSc預(yù)后：ILD vs. PAHPEKING UNION MEDICAL COLLEGE HOSPITALPAH是SLE的重要死因No.4 （13.8%）PEKING UNION MEDICAL COLLEGE HOSPITAL早期發(fā)現(xiàn)篩查CTDPAH？PEKING UNION M

12、EDICAL COLLEGE HOSPITAL改善預(yù)后的關(guān)鍵早期診治PEKING UNION MEDICAL COLLEGE HOSPITAL改善預(yù)后的關(guān)鍵早期診斷PEKING UNION MEDICAL COLLEGE HOSPITALCTD的確診可促使更早篩查PAHPEKING UNION MEDICAL COLLEGE HOSPITAL改善預(yù)后的關(guān)鍵早期診治PEKING UNION MEDICAL COLLEGE HOSPITAL高度警惕CTD/PAH相關(guān)的表觀特征雷諾現(xiàn)象&指端血管炎PEKING UNION MEDICAL COLLEGE HOSPITAL高度警惕CTD/PAH相關(guān)的血

13、清標(biāo)志抗RNP抗體PEKING UNION MEDICAL COLLEGE HOSPITALSLEPAH的相關(guān)危險(xiǎn)因素Rheumat Int. 2011, Mar 25. EpubPEKING UNION MEDICAL COLLEGE HOSPITALSLEPAH的相關(guān)危險(xiǎn)因素PEKING UNION MEDICAL COLLEGE HOSPITALPAH的早期篩查策略PEKING UNION MEDICAL COLLEGE HOSPITAL超聲心動(dòng)圖（TTE）右心導(dǎo)管（PAC） 胸部影像學(xué)：CXR、HRCT心電圖肺功能（通氣彌散）核素肺通氣/灌注顯像生化指標(biāo)心肌核磁共振CTDPAH的篩查和

14、評(píng)估6分鐘步行距離WHO 心功能分級(jí)PEKING UNION MEDICAL COLLEGE HOSPITAL胸部影像學(xué)PEKING UNION MEDICAL COLLEGE HOSPITAL胸部影像學(xué)PEKING UNION MEDICAL COLLEGE HOSPITAL心電圖檢查PEKING UNION MEDICAL COLLEGE HOSPITALPEKING UNION MEDICAL COLLEGE HOSPITAL肺功能測(cè)定PEKING UNION MEDICAL COLLEGE HOSPITAL肺功能測(cè)定FVC%/DLCO%比值肺間質(zhì)纖維化：FVC和DLCO同步下降 FVC

15、%/DLCO%1.8二者合并： FVC%/DLCO%1.41.8PEKING UNION MEDICAL COLLEGE HOSPITALPEKING UNION MEDICAL COLLEGE HOSPITALPEKING UNION MEDICAL COLLEGE HOSPITALPEKING UNION MEDICAL COLLEGE HOSPITALPEKING UNION MEDICAL COLLEGE HOSPITAL超聲心動(dòng)圖檢查PEKING UNION MEDICAL COLLEGE HOSPITAL超聲心動(dòng)圖檢查PEKING UNION MEDICAL COLLEGE HOS

16、PITAL根據(jù)PASP分為：輕度 4050mm Hg中度 5070mm Hg重度 70mm Hg肺動(dòng)脈高壓嚴(yán)重度PEKING UNION MEDICAL COLLEGE HOSPITALPEKING UNION MEDICAL COLLEGE HOSPITALPAH患者應(yīng)用右心導(dǎo)管的EBMIn patients with suspected PH, right-heart catheterization is required to confirm the presence of PH, establish the specific diagnosis, and determine the s

17、everity of PH.Quality of evidence: good; benefit; substantial; strength of recommendation: A.In patients with suspected PH, right-heart catheterization is required to guide therapy.Quality of evidence: low; benefit; substantial; strength of recommendation: B.McGoon, et al. ACCP Consensus CHEST 2004;

18、 126: 14S-34SPEKING UNION MEDICAL COLLEGE HOSPITALSWAN-GANZ肺動(dòng)脈內(nèi)熱稀釋漂浮導(dǎo)管PEKING UNION MEDICAL COLLEGE HOSPITAL0-88-1415-30PEKING UNION MEDICAL COLLEGE HOSPITAL肺動(dòng)脈導(dǎo)管的胸片定位PEKING UNION MEDICAL COLLEGE HOSPITAL血流動(dòng)力學(xué)計(jì)算體表面積（BSA）:查表計(jì)算 BSA=0.007184 * H0.725 * W0.425 (H cm, W kg)MAP=DAP+（SBP-DBP）/3SV = CO / HRS

19、VR = 79.9*（MAP-CVP）/CO PVR = 79.9*（MPAP-PAWP）/COLVSW = 0.0136 * 1.05 * SV *(MBP-CVP) RVSW = 0.0136 * 1.05 * SV *(MBP-CVP)指數(shù)：CI=CO/BSA, SVI=SV/BSA SVRI=TPR*BSA, PVRI=PVR*BSA LVSWI=LVSW/BSA, RVSWI=RVSW/BSAPEKING UNION MEDICAL COLLEGE HOSPITALCTDPAH的篩查PEKING UNION MEDICAL COLLEGE HOSPITALCTDPAH的確診PEKIN

20、G UNION MEDICAL COLLEGE HOSPITALPEKING UNION MEDICAL COLLEGE HOSPITALCTDPAH的診斷：Echo與RHCPEKING UNION MEDICAL COLLEGE HOSPITALPEKING UNION MEDICAL COLLEGE HOSPITALAVC與CCB長(zhǎng)期反應(yīng)性PEKING UNION MEDICAL COLLEGE HOSPITALPEKING UNION MEDICAL COLLEGE HOSPITALPEKING UNION MEDICAL COLLEGE HOSPITALPEKING UNION MED

21、ICAL COLLEGE HOSPITAL六分鐘步行試驗(yàn)6 minute walk test（6MWT）PEKING UNION MEDICAL COLLEGE HOSPITAL1. 試驗(yàn)環(huán)境沒有交通障礙的連續(xù)的跑道最小直線長(zhǎng)度以25米為限，可以30米距離標(biāo)記，掉轉(zhuǎn)方向標(biāo)志舒適的環(huán)境， 溫度和濕度PEKING UNION MEDICAL COLLEGE HOSPITAL2. 設(shè)備生命指標(biāo)監(jiān)測(cè)設(shè)備氧氣、急救藥物及器械供患者休息的椅子Borg Scale（呼吸困難分級(jí)指數(shù)）PEKING UNION MEDICAL COLLEGE HOSPITALPEKING UNION MEDICAL COLLE

22、GE HOSPITAL3. 試驗(yàn)準(zhǔn)備和解釋說明適合運(yùn)動(dòng)的衣履講解試驗(yàn)過程及作用，獲得受試者配合標(biāo)準(zhǔn)的語(yǔ)言 “ 您即將開始一個(gè)6分鐘步行試驗(yàn)。試驗(yàn)?zāi)繕?biāo)是在6分鐘內(nèi)以盡可能快的速度步行盡可能遠(yuǎn)的距離。試驗(yàn)過程中，如果有必要，可以減慢速度，甚至停下來(lái)，但一旦您停止步行，我們會(huì)希望您能盡快繼續(xù)步行。待我喊 開始 口令，您就開始步行，在步行過程中，不要講話，除非您有疑問。請(qǐng)問您現(xiàn)在有什么問題嗎？”PEKING UNION MEDICAL COLLEGE HOSPITAL4. 試驗(yàn)實(shí)施受試者聽到開始口令后立即開始步行需要時(shí)醫(yī)務(wù)人員可以在受試者身后輕輕步行定時(shí)告知剩余時(shí)間給予一些標(biāo)準(zhǔn)的鼓勵(lì)性話語(yǔ) PEKIN

23、G UNION MEDICAL COLLEGE HOSPITAL5.試驗(yàn)結(jié)束測(cè)試結(jié)束時(shí)，做標(biāo)記，測(cè)量長(zhǎng)度，記錄步行距離記錄SPO2 、HR、R、BP、受限癥狀和 Borg Scale試驗(yàn)結(jié)束，受試者至少應(yīng)在檢查室休息15分鐘PEKING UNION MEDICAL COLLEGE HOSPITAL安全措施試驗(yàn)地點(diǎn)試驗(yàn)前嚴(yán)格評(píng)估病情急救車和急救物品的準(zhǔn)備掌握基本甚至高級(jí)的復(fù)蘇技術(shù)PEKING UNION MEDICAL COLLEGE HOSPITAL 胸痛 難以忍受的呼吸困難 下肢痙攣 步履蹣跚 出虛汗 面色蒼白 SPO2下降，低 于85% 患者無(wú)法耐受安全措施：終止 6MWT 指征PEKIN

24、G UNION MEDICAL COLLEGE HOSPITAL對(duì)HF患者生存預(yù)后的評(píng)價(jià)SOLVD 研究和Roul等顯示， 6MWD 對(duì)CHF患者的死亡率和再入院率具有獨(dú)立的預(yù)測(cè)價(jià)值Bittner 等根據(jù)步行距離對(duì)6MWT分級(jí)： Level l ( 65002 )Ambrisentan Modestly ETA selective (ETA vs ETB preference ratio: 773 )內(nèi)皮素受體拮抗劑磷酸二酯酶途徑O2 / Alveolar VentilationNOSL-argininNOGunylate CyclasecGMPdegradationPDEcGMP-Kinas

25、eK+channel activationCa+channel inhabitionIntracellular Ca+VasodilatationPDE5 存在于肺血管床和視網(wǎng)膜PAH時(shí)PDE5 表達(dá)水平上調(diào)抑制PDE5 活性可以降低肺動(dòng)脈壓一種選擇性PDE5抑制劑2000年發(fā)現(xiàn)西地那非在兒童原發(fā)性肺動(dòng)脈高壓患者中可選擇性擴(kuò)張肺動(dòng)脈。西地那非選擇性PDE-5抑制劑VVVQNONONOcGMP/PDE5cGMP/PDE5cGMP/PDE5VQNONONOcGMP/PDE5cGMP/PDE5cGMP/PDE5西地那非cGMPcGMPcGMP西地那非的肺選擇性Ghofrani et al., Annals Int Med 2002Ghofrani et al., Lancet 2002 西地那非抗內(nèi)皮細(xì)胞增殖作用Schermuly et al., AJRCCM 2003Rondelet et al., Circulation 2004西地那非的作用機(jī)制 PDE5拮抗劑西地那非（sildenafil citrate，Viagra，萬(wàn)艾可/偉哥，輝瑞