结缔组织病相关肺动脉高压课件

1、结缔组织病相关肺动脉高压什么是肺动脉高压？PEKING UNION MEDICAL COLLEGE HOSPITALPEKING UNION MEDICAL COLLEGE HOSPITALPAH肺动脉高压的发病机制PEKING UNION MEDICAL COLLEGE HOSPITAL肺动脉高压=肺循环疾病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肺高压的“欧姆定律”肺动脉肺肌性小动脉肺毛细血管床肺小静脉肺静脉左心房肺动脉血栓和栓塞IPAH、FPAH、PPHN、CTD/HIV/门脉高压etc.左向右分流PVODPCHPaO2I型：DPLD/高原病/肺泡毛细血

5、管发育不良II型：COPD/OSAS左房或左室心脏病瓣膜病UIRCTD肺静脉受压肺动脉受压PEKING UNION MEDICAL COLLEGE HOSPITALPH（肺循环高压、肺动脉高压）：各种原因引起肺血管阻力进行性增高为特征的临床-病理生理综合征。导致右心负荷增大，右心功能不全引起的系列临床表现。PAH（动脉型肺动脉高压、肺动脉高压）：病变直接累及肺动脉并引起肺动脉结构和功能改变的肺动脉高压。 PEKING UNION MEDICAL COLLEGE HOSPITAL肺动脉高压定义PEKING UNION MEDICAL COLLEGE HOSPITAL结缔组织病发生PAH的机制孤立

6、的肺血管病变肺小血管炎肺小动脉血栓栓塞肺小血管收缩、舒张因子失衡肺血管痉挛（雷诺现象）继发于肺间质纤维化继发于心脏病变血栓栓塞肺间质纤维化PEKING UNION MEDICAL COLLEGE HOSPITALCTDPAH是一种常见的临床病理生理综合征PEKING UNION MEDICAL COLLEGE HOSPITALCTD是相关因素所致PAH的首要原因法国PAH注册登记研究PEKING UNION MEDICAL COLLEGE HOSPITALCTD是相关因素所致PAH的首要原因美国REVEAL注册研究Badesch DB, et al. Chest. 2010;137:376PE

7、KING UNION MEDICAL COLLEGE HOSPITALCTD是相关因素所致PAH的首要原因中国的注册研究PEKING UNION MEDICAL COLLEGE HOSPITALPAH是CTD不容忽视的合并症2.6%（日本，Yoshida S，2001）8% （USA，NIH，1987）3.7%（中国，北京协和医院，2006，82/2189）4.2%（中国，广东省人民医院，2009,79/1892）3.89% in SLE（中国，CSTAR，2011，77/1980）PEKING UNION MEDICAL COLLEGE HOSPITALPAH是CTD不容忽视的合并症PEKI

8、NG UNION MEDICAL COLLEGE HOSPITAL肺动脉高压（PAH）北京协和医院结缔组织病住院患者统计PAH是CTD不容忽视的合并症PEKING UNION MEDICAL COLLEGE HOSPITALCTDPAH构成的地域差异PEKING UNION MEDICAL COLLEGE HOSPITAL北京协和医院中华风湿病学杂志 1999 第1期中华内科杂志. 2006 Jun;45(6):467-71不同CTD中PAH的患病率广东省人民医院PEKING UNION MEDICAL COLLEGE HOSPITALPAH是CTD不容忽视的合并症中国患病率居世界各种族第二位

9、92.9/100,000估计中国狼疮患者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系统性红斑狼疮（SLE）的患病数具于首位PAH是CTD不容忽视的合并症PAH是严重影响CTD患者预后的危险因素PEKING UNION MEDICAL COLLEGE HOSPITALI类PAH

10、中不同原因的预后YearsCHDIPAHMcLaughlin VV, et al. Chest, 2004;126:78PEKING UNION MEDICAL COLLEGE HOSPITALCTD-PAH vs.IPAH：美国REVEAL研究Chung L, et al. Chest, 2010;138:13831年生存率和无住院率：IPAHCTD-PAHPEKING UNION MEDICAL COLLEGE HOSPITALCTD-PAH vs.IPAH：中国注册PEKING UNION MEDICAL COLLEGE HOSPITALPAH已成为SSc患者的主要死因中位生存时间1年1

11、年存活率为55%2年40-55%5年10%（不伴PAH的SSc为80%）PEKING UNION MEDICAL COLLEGE HOSPITALSSc-PAH vs.IPAHPEKING UNION MEDICAL COLLEGE HOSPITALProgress Cardio Dis, 2002; 45:225SSc预后：ILD vs. PAHPEKING UNION MEDICAL COLLEGE HOSPITALPAH是SLE的重要死因No.4 （13.8%）PEKING UNION MEDICAL COLLEGE HOSPITAL早期发现筛查CTDPAH？PEKING UNION M

12、EDICAL COLLEGE HOSPITAL改善预后的关键早期诊治PEKING UNION MEDICAL COLLEGE HOSPITAL改善预后的关键早期诊断PEKING UNION MEDICAL COLLEGE HOSPITALCTD的确诊可促使更早筛查PAHPEKING UNION MEDICAL COLLEGE HOSPITAL改善预后的关键早期诊治PEKING UNION MEDICAL COLLEGE HOSPITAL高度警惕CTD/PAH相关的表观特征雷诺现象&指端血管炎PEKING UNION MEDICAL COLLEGE HOSPITAL高度警惕CTD/PAH相关的血

13、清标志抗RNP抗体PEKING UNION MEDICAL COLLEGE HOSPITALSLEPAH的相关危险因素Rheumat Int. 2011, Mar 25. EpubPEKING UNION MEDICAL COLLEGE HOSPITALSLEPAH的相关危险因素PEKING UNION MEDICAL COLLEGE HOSPITALPAH的早期筛查策略PEKING UNION MEDICAL COLLEGE HOSPITAL超声心动图（TTE）右心导管（PAC） 胸部影像学：CXR、HRCT心电图肺功能（通气弥散）核素肺通气/灌注显像生化指标心肌核磁共振CTDPAH的筛查和

14、评估6分钟步行距离WHO 心功能分级PEKING UNION MEDICAL COLLEGE HOSPITAL胸部影像学PEKING UNION MEDICAL COLLEGE HOSPITAL胸部影像学PEKING UNION MEDICAL COLLEGE HOSPITAL心电图检查PEKING UNION MEDICAL COLLEGE HOSPITALPEKING UNION MEDICAL COLLEGE HOSPITAL肺功能测定PEKING UNION MEDICAL COLLEGE HOSPITAL肺功能测定FVC%/DLCO%比值肺间质纤维化：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超声心动图检查PEKING UNION MEDICAL COLLEGE HOSPITAL超声心动图检查PEKING UNION MEDICAL COLLEGE HOS

16、PITAL根据PASP分为：轻度 4050mm Hg中度 5070mm Hg重度 70mm Hg肺动脉高压严重度PEKING UNION MEDICAL COLLEGE HOSPITALPEKING UNION MEDICAL COLLEGE HOSPITALPAH患者应用右心导管的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肺动脉内热稀释漂浮导管PEKING UNION MEDICAL COLLEGE HOSPITAL0-88-1415-30PEKING UNION MEDICAL COLLEGE HOSPITAL肺动脉导管的胸片定位PEKING UNION MEDICAL COLLEGE HOSPITAL血流动力学计算体表面积（BSA）:查表计算 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)指数：CI=CO/BSA, SVI=SV/BSA SVRI=TPR*BSA, PVRI=PVR*BSA LVSWI=LVSW/BSA, RVSWI=RVSW/BSAPEKING UNION MEDICAL COLLEGE HOSPITALCTDPAH的筛查PEKING UNION MEDICAL COLLEGE HOSPITALCTDPAH的确诊PEKIN

20、G UNION MEDICAL COLLEGE HOSPITALPEKING UNION MEDICAL COLLEGE HOSPITALCTDPAH的诊断：Echo与RHCPEKING UNION MEDICAL COLLEGE HOSPITALPEKING UNION MEDICAL COLLEGE HOSPITALAVC与CCB长期反应性PEKING UNION MEDICAL COLLEGE HOSPITALPEKING UNION MEDICAL COLLEGE HOSPITALPEKING UNION MEDICAL COLLEGE HOSPITALPEKING UNION MED

21、ICAL COLLEGE HOSPITAL六分钟步行试验6 minute walk test（6MWT）PEKING UNION MEDICAL COLLEGE HOSPITAL1. 试验环境没有交通障碍的连续的跑道最小直线长度以25米为限，可以30米距离标记，掉转方向标志舒适的环境， 温度和湿度PEKING UNION MEDICAL COLLEGE HOSPITAL2. 设备生命指标监测设备氧气、急救药物及器械供患者休息的椅子Borg Scale（呼吸困难分级指数）PEKING UNION MEDICAL COLLEGE HOSPITALPEKING UNION MEDICAL COLLE

22、GE HOSPITAL3. 试验准备和解释说明适合运动的衣履讲解试验过程及作用，获得受试者配合标准的语言 “ 您即将开始一个6分钟步行试验。试验目标是在6分钟内以尽可能快的速度步行尽可能远的距离。试验过程中，如果有必要，可以减慢速度，甚至停下来，但一旦您停止步行，我们会希望您能尽快继续步行。待我喊 开始 口令，您就开始步行，在步行过程中，不要讲话，除非您有疑问。请问您现在有什么问题吗？”PEKING UNION MEDICAL COLLEGE HOSPITAL4. 试验实施受试者听到开始口令后立即开始步行需要时医务人员可以在受试者身后轻轻步行定时告知剩余时间给予一些标准的鼓励性话语 PEKIN

23、G UNION MEDICAL COLLEGE HOSPITAL5.试验结束测试结束时，做标记，测量长度，记录步行距离记录SPO2 、HR、R、BP、受限症状和 Borg Scale试验结束，受试者至少应在检查室休息15分钟PEKING UNION MEDICAL COLLEGE HOSPITAL安全措施试验地点试验前严格评估病情急救车和急救物品的准备掌握基本甚至高级的复苏技术PEKING UNION MEDICAL COLLEGE HOSPITAL 胸痛 难以忍受的呼吸困难 下肢痉挛 步履蹒跚 出虚汗 面色苍白 SPO2下降，低 于85% 患者无法耐受安全措施：终止 6MWT 指征PEKIN

24、G UNION MEDICAL COLLEGE HOSPITAL对HF患者生存预后的评价SOLVD 研究和Roul等显示， 6MWD 对CHF患者的死亡率和再入院率具有独立的预测价值Bittner 等根据步行距离对6MWT分级： Level l ( 65002 )Ambrisentan Modestly ETA selective (ETA vs ETB preference ratio: 773 )内皮素受体拮抗剂磷酸二酯酶途径O2 / Alveolar VentilationNOSL-argininNOGunylate CyclasecGMPdegradationPDEcGMP-Kinas

25、eK+channel activationCa+channel inhabitionIntracellular Ca+VasodilatationPDE5 存在于肺血管床和视网膜PAH时PDE5 表达水平上调抑制PDE5 活性可以降低肺动脉压一种选择性PDE5抑制剂2000年发现西地那非在儿童原发性肺动脉高压患者中可选择性扩张肺动脉。西地那非选择性PDE-5抑制剂VVVQNONONOcGMP/PDE5cGMP/PDE5cGMP/PDE5VQNONONOcGMP/PDE5cGMP/PDE5cGMP/PDE5西地那非cGMPcGMPcGMP西地那非的肺选择性Ghofrani et al., Annals Int Med 2002Ghofrani et al., Lancet 2002 西地那非抗内皮细胞增殖作用Schermuly et al., AJRCCM 2003Rondelet et al., Circulation 2004西地那非的作用机制 PDE5拮抗剂西地那非（sildenafil citrate，Viagra，万艾可/伟哥，辉瑞