2010_肺动脉高压指南
2010中国肺高血压诊治指南
2010中国肺高血压诊治指南前言肺高血压（pulmonary hypertension,PH）是一大类以肺动脉压力增高，伴或不伴有小肺动脉病变为特征的恶性肺血管疾病，往往引起右心功能衰竭甚至死亡[1]。
PH已成为一类严重威胁人类身心健康的常见疾病[2]。
近十余年来随着国内外对肺高血压流行病学和发病机制，病理学及病理生理学研究的深入，诊断评价手段的不断丰富，以及大规模临床治疗研究结果的公布，特别是2008年世界卫生组织基于近期肺高血压领域最新研究进展制定了第四次PH诊断和治疗指南，在此基础上2009年美国和欧洲均公布了更新后的肺动脉高压（pulmonary arterial hypertension,PAH）和PH指南或专家共识[3,4]。
这些诊疗指南和专家共识规范了临床医师的诊治行为，显著改善了PH患者的生活质量和预后。
我国2007年公布的中国肺动脉高压诊断与治疗专家共识基于2003年世界卫生组织肺高血压诊治指南制定，对提高我国临床医师诊断意识及整体诊治水平发挥了重要作用[5]。
欧美指南中更新的内容及近年来我国公布的肺动脉高压诊断和治疗临床研究结果均提示，我们有必要及时更新我国对于肺动脉高压和肺高压的指南文件，用于指导临床实践。
因此中华医学会心血管病分会肺血管病学组相关专家和中华心血管病杂志组织国内肺高压领域专家共同对我国指南进行修订更新。
为了便于读者了解某一诊疗方法的价值或意义，本指南对支持各诊疗方法循证医学证据等级，以国际通用的方式表达如下：Ⅰ类：已证实和(或)一致公认某诊疗措施有益、有用和有效。
Ⅱ类：某诊疗措施的有用性和有效性的证据尚有矛盾或存在不同观点。
Ⅱa类：有关证据和(或)观点倾向于有用和有效。
Ⅱb类：有关证据和(或)观点尚不能充分说明有用和有效。
Ⅲ类：已证实和(或)一致公认某诊疗措施无用和无效并在有些病例可能有害。
对证据来源的水平表达如下：证据水平A：资料来源于多项随机临床试验或荟萃分析。
肺动脉高压
3. 与肺疾病或缺氧相关的肺动脉高压 • 慢性阻塞性肺疾病 • 肺间质疾病 • 睡眠呼吸障碍 • 肺泡-毛细血管发育不良 4. 慢性血栓和/或栓塞性肺动脉高压 • 血栓栓塞近端肺动脉 • 血栓栓塞远端肺动脉 • 非血栓性肺栓塞
5. 混合性肺动脉高压
• 肺血管压迫，淋巴血管瘤病……
非特异的，早期可无症状，随病情进展可有如下表现： 1.呼吸困难:最早出现，也最常见。 2.疲劳、乏力、运动耐量减低. 3.晕 厥. 4.心绞痛或胸痛. 5.咯血. 6.声音嘶哑:肺动脉扩张压迫喉返神经所致. 7.右心衰的症状. 8.原发病的症状:如结缔组织病相关性肺动脉高压可有 脱发、光敏、口腔溃疡、关节炎等。 二、体征: 1.多与右心衰竭有关 ：紫绀 、颈静脉充盈或怒张 、P2亢进、 S3 ; 2.肺动脉高压特殊体征：上下肢的差异性紫绀（单独下肢出现杵 状趾而手指正常）。往往是诊断动脉导管未闭的重要线索 ；如果上下肢 均存在杵状指/趾往往提示已可诊断艾森曼格综合征。 3.鼻衄：往往提示 患者合并遗传性出血性毛细血管扩张症 ; 4.杂音：胸骨左缘喷射性杂 音并向右侧传导往往提示室间隔缺损等畸形的存在; 5.面部红斑，关节 畸形，外周血管杂音都是提示患者结缔组织疾病的征象 ; 5下肢静脉 血栓栓塞往往有腓肠肌压痛，且病侧下肢周径一般比对侧粗1厘米以上 •
肺高压的诊断分类
(2003年第三次WHO PAH工作组会议，威尼斯)
1. 肺动脉高压 • 特发性肺动脉高压 • 家族性肺动脉高压 • 相关因素所致 – 胶原血管病 – HIV 感染 – 门静脉高压 – 药物和毒物 – 先天性心脏病…… • 因肺静脉或毛细血管 • 病变导致的肺动脉高压 2. 主要累及左心的肺动脉高压 • 主要累及左房或左室的心脏疾病 • 左心瓣膜病
肺动脉高压治疗指南
肺动脉高压治疗指南肺动脉高压治疗指南肺动脉收缩压（pulmonary arterial systolic pressure，PASP）超过30mmHg或肺动脉平均压（pulmonary arterial mean pres-sure，PAMP）超过20mmHg时，即表示有肺动脉高压存在。
肺动脉高压治疗指南为2007年美国呼吸学会（ATS）会议上进行修订完成。
肺动脉高压（PAH）属于肺循环疾病中的一个重要类别。
肺动脉高压的临床分类标准于2003年威尼斯第三届世界肺动脉高压会议上进行了修订；美国胸科医师协会（ACCP）和欧洲心脏病协会（ESC）分别于2004年7月和12月制定了肺动脉高压的诊断和治疗指南。
2007年6月ACCP专家委员会在《Chest》上更新了肺动脉高压内科治疗指南，对加用原则和联合治疗提出了一些新观念。
2007年美国呼吸学会（ATS）会议进一步阐述了肺动脉高压2003年修订后的内容，现对肺动脉高压治疗指南作一解读。
肺动脉高压治疗指南可分为一般治疗、药物治疗、介入及手术治疗。
肺动脉高压治疗指南:一般治疗活动和旅行适当调整日常活动，可提高生活质量，减少症状。
体力活动强度不应过强。
避免在餐后、气温过高及过低情况下进行活动。
预防感染肺动脉高压易发生肺部感染，肺炎占总死亡原因的7%，因此应及早诊断、积极治疗。
推荐使用流感和肺炎球菌疫苗。
避孕、绝经期后激素替代治疗怀孕和分娩会使患者病情恶化。
育龄期妇女应采取适宜方法避孕。
若怀孕应及时终止妊娠。
降低血液黏度肺动脉高压患者长期处于低氧血症，往往出现红细胞增多症，红细胞比积升高。
当患者出现头痛、注意力不集中等症状，伴有红细胞比积超过65%时，可考虑放血疗法以降低血液黏度，增加血液向组织释放氧的能力。
肺动脉高压治疗指南抗凝治疗肺动脉高压患者容易发生肺动脉原位血栓形成，加重肺动脉高压，需要抗凝治疗。
常用口服抗凝剂华法林，一般认为国际化标准比值INR目标值为1.5～2.5。
2010 中国肺动脉高压指南
体征反应肺高压的程度
体征 S2亢进（>90%在心尖可明显听到） 收缩早期喀啦音 收缩中期喷射性杂音 胸骨左缘抬举感 右室S4音（38%）
颈静脉明显a 波
意义 高的肺动脉压导致肺动脉瓣关闭力量增加 肺动脉瓣向高压的肺动脉开发突然受阻 跨肺动脉瓣血流紊乱 右室压增高并肥大 右室压增高并肥大
右室顺应性明显减退
一般治疗
运动和康复训练、避孕、心理治疗、预防感染及择期手 术指导等多个方面，鼓励患者，增强其战胜疾病的信心。
支持治疗：抗凝、吸氧、利尿剂和地高辛。
对于有右心衰竭和水肿征象的PAH患者，应该给予利尿剂 ，控制液体入量，适当限制钠盐摄入，注意纠正电解质及 酸碱平衡紊乱； 对于特发性肺动脉高压、可遗传性肺动 脉高压及食欲抑制剂相关性肺动脉高压的患者，应该给予 口服抗凝剂的治疗.
需要强调与肺动脉高压相关疾病的特殊体征往往可 提示诊断
上下肢的差异性紫绀，是诊断动脉导管未闭的重要线索。 如果上下肢均存在杵状指/趾往往提示已可诊断艾森曼格 综合征。
鼻衄，口腔粘膜或体表皮肤毛细血管扩张往往提示患者合 并遗传性出血性毛细血管扩张症。
胸骨左缘喷射性杂音并向右侧传导往往提示室间隔缺损等 畸形的存在。
部分接受口服、吸人或静脉注射前列环素治
疗的患者，联合西地拉非或波生坦后疗效 更佳。另外，接受波生坦治疗的患者联合 吸人性依洛前列素后6分钟步行距离增加更 多。目前需要进行统计学效能更强的前瞻 性、随机、双盲、安慰剂对照研究，以确 立联合治疗对肺动脉高压的疗效。
介入及手术治疗
房间隔造瘘术 严重肺动脉高压的预后很大一部分取决于右心室
面部红斑，关节畸形，外周血管杂音都是提示结缔组织疾 病的征象。
下肢静脉血栓栓塞往往有腓肠肌压痛，且病侧下肢周径一 般比对侧粗1厘米以上。
肺动脉高压欧洲指南
欧洲心脏病学会肺动脉高压指南解读Eur Heart J,2010,25:2243-22781951年Dresdale等首先提出了原发性肺动脉高压（primary pulmonary hypertension，PPH）和继发性肺动脉高压的概念，此后对肺动脉高压的研究逐渐增多。
1973年世界卫生组织（WHO）主办了第一届原发性肺动脉高压国际研讨会。
当时会议回顾了十分有限的原发性肺动脉高压的研究，并就此病诊断治疗等未来发展方向达成共识。
1998年WHO 在法国Evian召开了第二次原发性肺动脉高压国际研讨会，制定了肺动脉高压临床分类标准。
新标准以病因为中心，具有很强的临床实用性，利于疾病的预防和治疗。
2003年WHO 在意大利的威尼斯又举行了第三次肺动脉高压专家工作组会议，根据近年研究成果以及对肺动脉高压认识的深入，对分类标准做了进一步修改，并以“特发性肺动脉高压”这一概念取代了“原发性肺动脉高压”。
30年间经过众多学者的努力，特别是近10年肺动脉高压这一领域发生了惊人变化，人们在遗传学、分子生物学、药物治疗以及外科技术等诸多领域都取得了进展。
这些进展促使新的、综合性更强的循证医学指南的问世。
如美国胸科医师学会（ACCP）发布的肺动脉高压的诊断和治疗：ACCP循证医学临床实践指南；欧洲心脏病学会（ESC）发布的肺动脉高压的诊断和治疗指南，对肺动脉高压的基础研究、诊断、治疗进行了全面阐述。
为了更好地理解和使用指南，在介绍指南正文前首先介绍指南中证据级别及诊断、治疗建议分级的制定原则。
建议等级：Ⅰ级有充分证据证实和（或）一致认为诊断程序和治疗是有益的、有用的和有效的Ⅱ级对治疗的有效性/有用性证据不一致和（或）意见有分歧Ⅱa级证据/意见支持有用/有效Ⅱb级对治疗的有效性/有用性没有肯定证据和（或）意见Ⅲa级有充分证据证实和（或）一致认为治疗无效，而且在某些病例甚至是有害的ａESC不建议级别Ⅲ的使用证据级别：A 证据来源于多中心随机对照临床试验或荟萃分析B 证据来源于单中心随机对照临床试验或大规模非随机研究C 证据来源于小规模研究、回顾性研究、病例注册登记以及专家共识下面就ESC肺动脉高压诊断和治疗指南（简称指南）作一简要介绍。
2010ESC成人先心病治疗指南
2010ESC成人先心病治疗指南抗生素使用原则为防止滥用抗生素导致细菌耐药，建议预防性抗生素仅限制性用于：①采用人工瓣膜或假体材料进行瓣膜修饰者；②有感染性心内膜炎病史者；③紫绀性先心病未行手术、有术后残余分流及行姑息性手术者；④先心病患者置入假体材料术后6个月；⑤在置入假体材料后仍有残余分流者。
肺动脉高压的靶向治疗肺动脉高压的靶向治疗是该指南的亮点之一，指南建议：①先心病肺动脉高压靶向治疗须在专门心脏中心进行（Ⅰ/C）；②内皮素受体拮抗剂波生坦（Bosentan）应首先用于WHO功能分级3级的艾森曼格综合征（Ⅰ/B）；③其他内皮素受体拮抗剂、5型磷酸二酯酶抑制剂、前列腺素可用于WHO功能分级3级的艾森曼格综合征（Ⅱa/C）；④可联合治疗WHO功能分级3级的艾森曼格综合征（Ⅱb/C）；⑤艾森曼格综合征应避免应用钙拮抗剂（Ⅲ/C）。
介入治疗建议房间隔缺损1.ASD介入并发症发生率＜1%，多为一过性房性心律失常，心房壁、主动脉壁破损和血栓事件较罕见，术后抗血小板治疗（阿司匹林）>6个月。
2.该指南推荐：①当存在显著分流、右室容量负荷过重和肺血管阻力＜5伍德（Wood）时，无论患者有无症状，应行介入封堵治疗（Ⅰ/B）；②继发孔ASD应行封堵器封堵（Ⅰ/C）；③怀疑为反常栓塞的ASD，无论缺损大小均应介入治疗（Ⅱa/C）；④肺血管阻力≥5Wood、＜2/3体循环阻力或肺动脉压＜2/3体循环血压（基线、应用血管扩张剂或选择性降低肺动脉压后）及以左向右分流为主时，可行介入治疗（Ⅱb/C）；⑤合并艾森曼格综合征时不宜行ASD封堵术（Ⅲ/C）。
室间隔缺损经导管封堵室间隔缺损（VSD）可用于手术风险大或已行多次手术的患者。
经导管封堵肌部VSD可作外科手术的替代选择，经导管封堵膜周部VSD被证实是可行的，但也有出现房室传导阻滞、三尖瓣和主动脉瓣反流的报告。
该指南对VSD经导管封堵有较为严格的适应证。
我国情况有所不同，国产与进口VSD封堵器的形态结构明显不同，介入封堵术后房室传导阻滞的发生率极低。
肺高压指南——肺动脉高压的评价
肺高压指南——肺动脉高压的评价上海远大心胸医院专家介绍，肺动脉高压指南————肺动脉高压的评价，一旦肺动脉高压的诊断成立，就应进一步检查，明确其所属类型，评估患者的运动耐量以及血流动力学情况。
（一）血液学检查和免疫学检查————肺动脉高压指南血常规、血生化、甲状腺功能检查应作为常规检查，而且应筛查有无易栓症，包括抗磷脂抗体检查，即狼疮抗凝物和抗心磷脂抗体。
CTD的诊断主要根据临床和实验室检查。
免疫组化检查包括抗核抗体、抗SCL70和RNP。
大约1／3的IPAH 患者呈现阳性，但抗核抗体滴度低（≤1：80稀释度）。
抗核抗体滴度有意义升高和（或）有可疑的CTD临床征象的患者都应进一步行血清学检查和风湿科会诊。
此外，所有患者都应在征得同意后行HIV的血清学检查。
（二）腹部超声————肺动脉高压指南腹部超声可以可靠地排除肝硬化和（或）门脉高压。
还可鉴别门脉高压的原因是右心衰竭抑或肝硬化所致。
（三）运动耐量————肺动脉高压指南客观评估患者的运动耐量，对于判定病情严重程度和治疗效果有重要意义。
最常用检查包括：六分钟步行试验（6MWT）和心肺运动试验。
6MWT简单易行且经济，其结果与NYHA分级负相关，并能预测IPAH患者的预后。
6MWT通常与Borg评分共同评估劳力性呼吸困难的程度。
有研究显示在随访26个月（中位数）时六分钟步行测试中如动脉血氧饱和度降低＞10%则死亡危险增加2．9倍。
此外，6MWT也是肺动脉高压大规模随机对照临床试验贯常采用的主要试验终点。
上海远大心胸医院专家指出，心肺运动试验通过测量运动时的肺通气和气体交换，能够提供更多的病理生理信息。
PAH 患者峰值氧耗、最大做功、无氧阈及峰值氧脉搏降低；而代表无效通气的VE／VCO2斜率增加。
峰值氧耗与患者的预后相关。
心肺运动试验最近在几个多中心试验中采用，但它在反映病情好转方面不及6MWT，据分析可能与其操作复杂有关，或是因为它对于亚极量运动耐量变化的灵敏性较差。
肺动脉高压指南
❖ 国内开展临床研究的初步结果也证实法舒地 尔静脉注射对PAH患者的急性血流动力学影 响与吸入伊洛前列素相似。
第十四页，共29页。
其它治疗
❖ NO吸入治疗，因无法监测吸入浓度，不便长 期应用，因此缺乏长期应用的临床资料。国 内外均不建议将其作为长期治疗药物。
了肺动脉高压（PAH）的治疗流程
J Am Coll Cardiol. 2013 Dec 24;62(25 Suppl):D60-72.
第十六页，共29页。
2014年肺动脉高压治疗流程
❖ 自1998年以来，PAH治疗方案变得越来越复杂。
❖ 至2003年，PAH治疗方案发展到5种药物，分为前列腺素、
内皮素受体拮抗剂（ERA）和磷酸二酯酶5抑制剂 （PDE-5I）三大类，包括口服、吸入、皮下注射和静脉
❖ IPAH患者中仅约10%急性肺血管扩张试验呈阳性，阳性患者
可以口服CCBs治疗。但治疗12个月后需复查急性肺血管扩 张试验，以判断患者对CCBs是否持续敏感。
第八页，共29页。
CCB
❖ 只有急性肺血管扩张试验结果阳性的患者才 能从CCBs治疗中获益
❖ CCBs有导致体循环血压下降、矛盾性肺动脉 压力升高、心功能衰竭加重、诱发肺水肿等 危险
肺动脉高压指南
第一页，共29页。
肺动脉高压（ PAH）简介
❖ PAH是累及肺动脉内皮细胞、肌层及外膜等的一种病变，使肺动脉血流受
限，从而导致肺血管阻力增加，最终引发右心衰竭的综合征。
第二页，共29页。
是确诊肺
Chest. 2004,126:14-34
第三页，共29页。
诊断标准
中国肺动脉高压指南PPT课件
概念
肺高血压（Pulmonary Hypertension）是指任何系统或者局 部病变而引起的肺循环血压增高，包括肺动脉高压，肺静 脉高压，混合性肺高压。
肺动脉高压(Pulmonary Arterial Hypertension)是指孤立的肺 动脉血压增高，肺静脉压力应正常，主要原因是肺小动脉 原发病变而导致的肺动脉阻力增加。
Humbert M, et al. Pulmonary arterial hypertension in France: results from a national registry. Am J Respir Crit Care Med. 2006;173:1023–30.
5
流行病学：NIH Registry Data
肺动脉高压: 除了上述肺高压的标准之外，尚需包括肺毛细 血管嵌顿压（PCWP）<15 mmHg
8
肺动脉高压的症状包括气短、乏力、疲劳
、心绞痛、晕厥和腹胀，疾病晚期患者休 息时上述症状无改善。
肺动脉高压的体征包括左胸抬高、第二心
音肺动脉瓣成分增强、三尖瓣关闭不全导 致的全收缩期杂音及肺动脉瓣关闭不全产 生的舒张期杂音。疾病晚期还可出现颈静 脉怒张、肝脏肿大、下肢水肿、腹腔积液 及四肢发冷等。 肺部听诊一般正常。 另外，在诊断其他疾病时发现心电图、x线 胸片或超声心动图异常时也可发现疑似肺 动脉高压的患者。
吸气时下腔静脉大小: 完全塌陷 RAP= 5 mmHg; 部分塌陷 RAP = 10 mmHg; 无塌陷 RAP = 15 mmHg
中国肺动脉高压指南
1
概念 流行病学 诊断 临床表现 治疗 护理
内容
2
肺动脉高压(pulmonary arterial hypertension， PAH)是各种原因引起的静息状态下右心导 管测得的肺动脉平均压≥25mmHg的一组临 床病理生理综合征,是一种以血管增殖和重 塑为特征的肺小动脉疾病，肺血管阻力往 往进行性升高，最终导致右心功能衰竭甚 至死亡。
肺动脉高压症治疗指南
指南的制定和推广有助于促进国内外专家之间的学术交流与合作，推 动肺动脉高压症治疗领域的进步。
未来研究方向和趋势
深入研究发病机制
针对肺动脉高压症的发病机制进行深入研究，有助于发现新的治 疗靶点和药物。
开展临床试验和转化研究
通过大规模、多中心的临床试验和转化研究，验证新药物和治疗方 法的疗效和安全性。
提高生活质量
良好的心理状态有助于提高患者的 生活质量，促进康复。
家属参与和支持
家属教育
对家属进行肺动脉高压症相关知识的 教育，使其了解患者的病情和治疗方 案。
家属参与护理
指导家属参与患者的日常护理，如协 助患者进行康复训练、提供营养支持 等。
家属支持
鼓励家属给予患者情感上的支持，关 心患者的心理需求，共同应对疾病带 来的挑战。
PART 06
总结与展望
REPORTING
治疗指南的意义和价值
提供规范化治疗建议
肺动脉高压症治疗指南为临床医生提供了基于最新研究和临床经验 的规范化治疗建议，有助于提高治疗效果和患者生活质量。
降低治疗风险
通过遵循指南推荐的治疗方法，可以减少不必要的药物使用和手术 干预，从而降低治疗过程中的风险。
PART 02
药物治疗
REPORTING
钙通道阻滞剂
作用机制
通过阻止钙离子进入肺动脉平滑肌细胞，降低肺动脉血管张力， 从而改善肺动脉高压。
常用药物
硝苯地平、地尔硫䓬等。
注意事项
需密切监测血压和心率，避免低血压和心动过缓等副作用。
前列环素类药物
01
02
03
作用机制
通过激活肺动脉平滑肌细 胞内的环磷酸腺苷（ cAMP）途径，降低肺动 脉血管张力，改善肺动脉 高压。
肺动脉高压诊疗指南共67页文档
ቤተ መጻሕፍቲ ባይዱ
肺动脉高压诊疗指南
11、战争满足了，或曾经满足过人的 好斗的 本能， 但它同 时还满 足了人 对掠夺 ，破坏 以及残 酷的纪 律和专 制力的 欲望。 ——查·埃利奥 特 12、不应把纪律仅仅看成教育的手段 。纪律 是教育 过程的 结果， 首先是 学生集 体表现 在一切 生活领 域—— 生产、 日常生 活、学 校、文 化等领 域中努 力的结 果。— —马卡 连柯(名 言网)
13、遵守纪律的风气的培养，只有领 导者本 身在这 方面以 身作则 才能收 到成效 。—— 马卡连 柯 14、劳动者的组织性、纪律性、坚毅 精神以 及同全 世界劳 动者的 团结一 致，是 取得最 后胜利 的保证 。—— 列宁 摘自名言网
15、机会是不守纪律的。——雨果
66、节制使快乐增加并使享受加强。 ——德 谟克利 特 67、今天应做的事没有做，明天再早也 是耽误 了。——裴斯 泰洛齐 68、决定一个人的一生，以及整个命运 的，只 是一瞬 之间。 ——歌 德 69、懒人无法享受休息之乐。——拉布 克 70、浪费时间是一桩大罪过。——卢梭
肺动脉高压指南
02
诊断流程
初步评估
初步病史和体格检查
了解患者症状、体征及家族史，检查包括测量血压、心率、呼吸 频率等。
心电图
显示心脏节律和电活动，帮助判断心脏病变。
X线胸片
观察肺部和心脏的形态，评估肺动脉高压的严重程度。
详细检查
01
一氧化氮合酶是一种能够合成一氧化氮的酶，一氧化氮能够扩张血管
和抑制炎症反应，针对一氧化氮合酶的新药能够提高体内一氧化氮的
含量，从而降低肺动脉压力。
基因治疗
基因治疗是一种通过改变基因来治疗疾病的方法，针对肺动脉高压的基 因治疗主要通过抑制导致肺动脉高压的基因的表达，从而降低肺动脉压 力。
针对内皮细胞功能的基因治疗：这种治疗方法主要是通过抑制导致内皮 细胞功能异常的基因的表达，从而改善内皮细胞的功能，降低肺动脉压
复受损的血管。
脐带血干细胞治疗：这种治疗方法主 要是通过将脐带血中的干细胞移植到 受损的肺血管中，利用干细胞的分化
能力来修复受损的血管。
06
PAH患者组织心理指南
患者支持系统
患者支持小组
提供患者支持小组，让患者可以相互交流、分享 经验，减轻孤独感。
肺动脉高压协会
建立肺动脉高压协会，提供患者教育和支持，帮 助患者更好地管理疾病。
力。
针对前列环素合成的基因治疗：这种治疗方法主要是通过增加前列环素 合成的基因的表达，从而增加体内前列环素的含量，降低肺动脉压力。
细胞治疗
细胞治疗是一种通过利用细胞来治疗 疾病的方法，针对肺动脉高压的细胞 治疗主要是通过利用干细胞来修复受 损的肺血管，从而降低肺动脉压力。
骨髓干细胞治疗：这种治疗方法主要 是通过将骨髓干细胞移植到受损的肺 血管中，利用干细胞的分化能力来修
肺动脉高压指南
ESC GuidelinesGuidelines on diagnosis and treatment of pulmonary arterial hypertensionThe Task Force on Diagnosis and Treatment of Pulmonary Arterial Hypertension of the European Society of CardiologyTask Force members:Nazzareno Galie`(Chairperson)1(Italy),Adam Torbicki (Poland),Robyn Barst (USA),Philippe Dartevelle (France),Sheila Haworth (UK),Tim Higenbottam (UK),Horst Olschewski (Germany),Andrew Peacock (UK),Giuseppe Pietra (Switzerland),Lewis J.Rubin (USA),Gerald Simonneau (Co-Chairperson)(France)ESC Committee for Practice Guidelines (CPG):Silvia G.Priori (Chairperson)(Italy),Maria Angeles Alonso Garcia (Spain),Jean-Jacques Blanc (France),Andrzej Budaj (Poland),Martin Cowie (UK),Veronica Dean (France),Jaap Deckers (The Netherlands),Enrique Fernandez Burgos (Spain),John Lekakis (Greece),Bertil Lindahl (Sweden),Gianfranco Mazzotta (Italy),Keith McGregor (France),Joa˜o Morais (Portugal),Ali Oto (Turkey),Otto A.Smiseth (Norway)Document reviewers:Gianfranco Mazzotta (CPG Review Coordinator)(Italy),Joan Albert Barbera (Spain),Simon Gibbs (UK),Marius Hoeper (Germany),Marc Humbert (France),Robert Naeije (Belgium),Joanna Pepke-Zaba (UK)Table of ContentsIntroduction.........................2245Clinical classification of pulmonary hypertension .2245Idiopathic pulmonary arterial hypertension ...2246Risk factors and associated conditions ......2246Pulmonary veno-occlusive disease andpulmonary capillary hemangiomatosis .....2247Classification of congenital systemic-to-pulmonary shunts ...............2247Pathology of pulmonary arterial hypertension ...2248Pulmonary arteriopathy ...............2248Pulmonary occlusive venopathy ..........2248Pulmonary microvasculopathy ...........2249Pathogenesis of pulmonary arterial hypertension .2249Diagnostic strategy ....................2250Clinical suspicion of pulmonary hypertension ..2251Detection of pulmonary hypertension.......2251ECG ..........................2251Chest radiograph..................2251Transthoracic Doppler-echocardiography (TTE).........................2251Pulmonary hypertension clinical classidentification ......................2252Pulmonary function tests and arterialblood gases .....................2252Ventilation and perfusion (V/Q)lung scan..2252High resolution CT of the lung (2252)Contrast enhanced spiral CT of the lung,pulmonary angiography andmagnetic resonance imaging ..........2252Pulmonary arterial hypertension evaluation (type,exercise capacity,hemodynamics)....2253Blood tests and immunology ..........2253Abdominal ultrasound scan ...........2253Exercise capacity .................22530195-668X/$-see front matterc 2004The European Society of Cardiology.Published by Elsevier Ltd.All rights reserved.doi:10.1016/j.ehj.2004.09.0141Corresponding author.Nazzareno Galie `,MD,Institute of Cardiology,University of Bologna,Via Massarenti,9,40138Bologna,Italy.Tel.:+39051349858;fax:+39051344859.E-mail addresses:n.galie@tuno.it,amanes@orsolamalpighi.med.unibo.it (N.Galie `)European Heart Journal (2004)25,2243–2278Hemodynamics (2253)Lung biopsy (2254)Assessment of severity (2254)Clinical variables (2254)Exercise capacity (2254)Echocardiographic parameters (2255)Hemodynamics (2255)Blood tests (2255)Treatment (2256)Introduction to level of evidence and grade of recommendation (2256)General measures (2256)Physical activity (2257)Travel/altitude (2258)Prevention of infections (2258)Pregnancy,birth control andpost-menopausal hormonal therapy (2258)Haemoglobin levels (2258)Concomitant medications (2258)Psychological assistance (2258)Elective surgery (2258)Pharmacological treatment (2259)Oral anticoagulant treatment (2259)Diuretics (2259)Oxygen (2259)Digitalis and dobutamine (2259)Calcium-channel blockers (2260)Synthetic prostacyclin and prostacyclinanalogues (2260)Epoprostenol (2260)Treprostinil (2262)Sodium beraprost (2262)Inhaled Iloprost (2263)Intravenous Iloprost (2263)Endothelin-1receptor antagonists (2263)Bosentan (2263)Sitaxsentan (2264)Ambrisentan (2265)Type5phosphodiesterase inhibitors (2265)Sildenafil (2265)Combination therapy (2265)Interventional procedures (2265)Balloon atrial septostomy (2265)Lung transplantation (2266)Treatment algorithm (2266)Specific conditions (2268)Paediatric pulmonary arterial hypertension (2268)Pulmonary arterial hypertension associated with Eisenmenger syndrome (2269)Porto-pulmonary hypertension (2269)Pulmonary arterial hypertension associatedwith HIV infection (2270)Pulmonary arterial hypertension associated with connective tissue diseases (2271)Pulmonary veno-occlusive disease andpulmonary capillary haemangiomatosis (2272)Acknowledgements (2273)Appendix A.List of Abbreviations (2273)References (2273)PreambleGuidelines and Expert Consensus Documents aim to present all the relevant evidence on a particular issue in order to help physicians to weigh the benefits and risks of a particular diagnostic or therapeutic proce-dure.They should be helpful in everyday clinical deci-sion-making.A great number of Guidelines and Expert Consensus Documents have been issued in recent years by the European Society of Cardiology(ESC)and by different organisations and other related societies.This profu-sion can put at stake the authority and validity of guidelines,which can only be guaranteed if they have been developed by an unquestionable decision-making process.This is one of the reasons why the ESC and others have issued recommendations for formulating and issuing Guidelines and Expert Consensus Documents.In spite of the fact that standards for issuing good quality Guidelines and Expert Consensus Documents are well defined,recent surveys of Guidelines and Expert Consensus Documents published in peer-reviewed jour-nals between1985and1998have shown that methodo-logical standards were not complied with in the vast majority of cases.It is therefore of great importance that guidelines and recommendations are presented in formats that are easily interpreted.Subsequently,their implementation programmes must also be well con-ducted.Attempts have been made to determine whether guidelines improve the quality of clinical practice and the utilisation of health resources.The ESC Committee for Practice Guidelines(CPG) supervises and coordinates the preparation of new Guidelines and Expert Consensus Documents produced by Task Forces,expert groups or consensus panels.The chosen experts in these writing panels are asked to pro-vide disclosure statements of all relationships they may have which might be perceived as real or potential con-flicts of interest.These disclosure forms are kept onfile at the European Heart House,headquarters of the ESC. The Committee is also responsible for the endorsement of these Guidelines and Expert Consensus Documents or statements.2244ESC GuidelinesThe Task Force has classified and ranked the useful-ness or efficacy of the recommended procedure and/or treatments and the Level of Evidence as indicated in IntroductionPulmonary arterial hypertension (PAH)is defined as a group of diseases characterised by a progressive increase of pulmonary vascular resistance (PVR)leading to right ventricular failure and premature death.1The median life expectancy from the time of diagnosis in patients with idiopathic PAH (IPAH),formerly known as primary pul-monary hypertension (PPH),before the availability of dis-ease-specific (targeted)therapy,was 2.8years through the mid-1980s.2PAH includes IPAH 3and pulmonary hypertension associated with various conditions such as connective tissue diseases (CTD),congenital systemic-to-pulmonary shunts,portal hypertension and Human Immunodeficiency Virus (HIV)infection.4All these condi-tions share equivalent obstructive pathological changes of the pulmonary microcirculation 5,6suggesting shared pathobiological processes among the disease spectrum of PAH.7In the past decade,we have witnessed major ad-vances in our understanding of the mechanism of disease development,in the diagnostic process,and in the treat-ment of PAH.The identification of mutations in the bone morpho-genetic protein receptor 2(BMPR2)in the majority of cases of familial PAH (FPAH)has been a major ad-vance in the elucidation of the pathogenic sequencein PAH.8,9A variety of cellular abnormalities have been described in the pulmonary vasculature of af-fected patients that may play important roles in the development and progression of PAH.7These include pulmonary endothelial dysfunction 10characterised by altered synthesis of nitric oxide,thromboxane A2,prostacyclin and endothelin,impaired potassium chan-nels and altered expression of the serotonin trans-porter in the smooth muscle cells and enhanced matrix production in the adventitia.7The diagnosis is now more clearly defined according to a new clinical classification and with consensus reached on algorithms of various investigative tests and proce-dures that exclude other causes and ensure an accurate diagnosis of PAH.11In addition,non-invasive markers of disease severity,either biomarkers or physiological tests that can be widely applied,have been proposed to reli-ably monitor the clinical course.11,12Finally,the numerous controlled clinical trials performed recently in PAH can allow us to abandon a clin-ical-based treatment strategy and adopt an evidence-based therapy that includes new classes of drugs such as prostanoids,13endothelin receptor antagonists 14and type 5phosphodiesterase inhibitors.15The present guidelines are intended to provide clear and concise indications for the practical use of the new clinical classification,and a brief description of the new pathological classification and of the recent patho-genetic insights.The diagnostic process will be discussed in order to propose a logical sequence of investigations for aetiology identification,disease assessment and fol-low-up.Special emphasis will be devoted to the evi-dence-based treatment algorithm that has been defined according to the ESC proposals for the Level of Evidence classification and the Grade of Recommendation 16for the available therapies.Clinical classification of pulmonary hypertensionPulmonary hypertension (PH)is defined by a mean pul-monary artery pressure (PAP)>25mmHg at rest or >30mmHg with exercise.17Current classification of PH is pre-sented in Table 1.It is a result of extensive discussion and represents a consensus accommodating our present understanding of pathophysiology as well as of clinical-based differences or similarities within PH.Understand-ing and correct clinical application of the classification should be aided by the following discourse.PH was previously classified into 2categories:PPH or secondary PH depending on the absence or the presence of identifiable causes or risk factors.3,17The diagnosis of PPH was one of exclusion after ruling out all causes of PH.In 1998,during the Second World Meeting on PH held in Evian –France,a clinical-based classification of PH was proposed.18The aim of the ‘‘Evian classification’’was to individualise different categories sharing similar-ities in pathophysiological mechanisms,clinical presen-tation and therapeutic options.Such a clinicalESC Guidelines 2245classification is essential in communicating about individ-ual patients,in standardising diagnosis and treatment,in conducting trials with homogeneous groups of patients, and lastly in analysing novel pathobiological abnormali-ties in well characterised patient populations.Obviously, a clinical classification does not preclude other classifi-cations such as a pathological classification based on his-tologicalfindings,or a functional classification based on the severity of symptoms.The2003Third World Sympo-sium on PAH held in Venice–Italy provided the opportu-nity to assess the impact and the usefulness of the Evian classification and to propose some modifications.It was decided to maintain the general architecture and philosophy of the Evian classification.However, some modifications have been proposed,mainly:to abandon the term‘‘primary pulmonary hypertension–PPH’’and to replace it with‘‘idiopathic pulmonary arte-rial hypertension–IPAH’’,to reclassify pulmonary veno-occlusive disease(PVOD)and pulmonary capillary haemangiomatosis(PCH),to update risk factors and associated conditions for PAH,and to propose some guidelines in order to improve the classification of con-genital systemic-to-pulmonary shunts(Table1).The aim of these modifications was to make the‘‘Venice clin-ical classification’’more comprehensive,easier to follow and widespread as a tool.Idiopathic pulmonary arterial hypertensionThe term PPH was retained in the Evian classification because of its common use and familiarity,and because it was emblematic of50years of intense scientific and clinical research.However,the use of the term‘‘pri-mary’’facilitated the reintroduction of the term‘‘sec-ondary’’that was abandoned in the Evian version because it was used to describe very heterogeneous conditions.In order to avoid any possible confusion in Venice it was decided that thefirst category termed ‘‘pulmonary arterial hypertension–PAH’’should in-clude three main subgroups:[1.1]idiopathic pulmonary arterial hypertension–IPAH,[1.2]familial pulmonary arterial hypertension–FPAH and[1.3]pulmonary arte-rial hypertension related to risk factors or associated conditions–APAH.Risk factors and associated conditionsA risk factor for PH is any factor or condition that is sus-pected to play a predisposing or facilitating role in the development of the disease.Risk factors may include drugs and chemicals,diseases or phenotype(age,gen-der).The term of‘‘associated conditions’’is usedwhen 2246ESC Guidelinesa statistically significantly increased incidence of PAH is found with a given predisposing factor,without,how-ever,meeting‘‘Koch’s postulate’’for causal relation-ship.Since the absolute risk of known risk factors for PAH is generally low,individual susceptibility or genetic predisposition is likely to play an important role.During the Evian meeting in1998,different risk factors and associated conditions were categorised according to the strength of their association with PH and their prob-able causal role.‘‘Definite’’indicates an association based on several concordant observations including a major controlled study or an unequivocal epidemic.‘‘Very likely’’indicates several concordant observations (including large case series and studies)that are not attributable to identified causes.‘‘Possible’’indicates an association based on case series,registries or expert opinions.‘‘Unlikely’’indicates risk factors that were sus-pected but for which controlled studies failed to demon-strate any association.According to the strength of the evidence,Table2 summarises,risk factors and associated conditions al-ready known19and novel‘‘possible’’risk factors for PAH that were identified recently,according to several case series or case reports.The new possible risk factors include haematological conditions such as asplenia sec-ondary to surgical splenectomy,20sickle cell disease,21 b-thalassaemia22and chronic myeloproliferative disor-ders23(polycythaemia vera,essential thrombocytaemia and myelofibrosis with myeloid metaplasia accompanying chronic myeloid leukaemia or the myelodysplastic syn-drome).Possible risk factors include also rare genetic or metabolic diseases such as type1a glycogen storage disease(Von Gierke disease),24Gaucher’s disease25and hereditary haemorrhagic telangiectasia(Osler–Weber–Rendu disease).26Pulmonary veno-occlusive disease and pulmonary capillary haemangiomatosisIn the Evian classification,PVOD was included in the pulmonary venous hypertension category that consists predominantly of left-sided heart diseases and PCH was included in the last and heterogeneous group of PH caused by diseases that directly affect the pulmon-ary vasculature.The similarities in the pathological features and clinical presentation,along with the pos-sible occurrence of pulmonary oedema during epo-prostenol therapy,suggest that these disorders mayoverlap.Accordingly,it seems logical to include PVOD and PCH within the same group,most appropriately within the category of PAH.In fact,the clinical pre-sentation of PVOD and PCH is generally similar to that of IPAH and the risk factors or conditions associated with PAH and PVOD/PCH are similar and include the scleroderma spectrum of the disease,HIV infection, and the use of anorexigens.Thus,in the new clinical classification(Table1),the PAH Clinical classification group1includes another subgroup termed PAH associ-ated with significant venous or capillary involvement (Clinical class1.4).Classification of congenitalsystemic-to-pulmonary shuntsThe proposed classification of congenital systemic-to-pulmonary shunts takes into account the type and the dimensions of the defect,the presence of associated extracardiac abnormalities and the correction status(Ta-ble3).All these factors are relevant for the development of PH and Eisenmenger physiology and the prognosis.Eisenmenger syndrome can be caused by simple or complex(about30%of cases)congenital heart defects.27ESC Guidelines2247Among simple defects,ventricular septal defects appear to be the most frequent,followed by atrial septal defects and patent ductus arteriosus.27It is calculated that10%of patients with ventricular septal defects of any size that are older than2years can develop Eisenmenger syndrome as compared to4–6%of subjects with atrial septal de-fects.28,29For patients with large defects,almost all cases with truncus arteriosus,50%of cases with ventricu-lar septal defects and10%of those with atrial septal de-fects will develop PAH and pulmonary vascular disease.30 In patients with atrial septal defects,those with sinus venosus defects have an higher incidence of PAH(16%) as compared to ostium secundum defects(4%).31 The development of PAH with pulmonary vascular dis-ease appears to be related to the size of the defect.In fact,with small-to moderate-size ventricular septal de-fects only3%of patients develop PH.32,33In contrast with larger defects(>1.5cm in diameter),50%will be affected. In case of small defects(ventricular septal defects<1cm and atrial septal defects<2cm of effective diameter as-sessed by echo)the exact pathophysiological role of the heart defect on the development of PAH is unknown.In some patients severe PAH can be detected after ‘‘successful’’correction of the heart defect.In many of these cases it is not clear if irreversible pulmonary vascular lesions were already present before the surgical interven-tion or if the pulmonary vascular disease has progressed despite a successful ually an early correc-tion prevents the subsequent development of PAH. Pathology of pulmonary arterial hypertensionPAH includes various forms of PH of different aetiologies but similar clinical presentation,and in many cases sim-ilar response to medical treatment.Histopathological changes in various forms of PAH are qualitatively similar5 but with quantitative differences in the distribution and prevalence of pathological changes in the different com-ponents of the pulmonary vascular bed(arterioles,capil-laries or veins).The following updated pathological classification has been proposed at the Third World Sym-posium on PAH of Venice(Table4).6Pulmonary arteriopathyThe main histopathological features of pulmonary arteri-opathy include medial hypertrophy,intimal thickening, adventitial thickening and complex lesions.Medial hypertrophy is an increase in the cross sec-tional area of the media of pre and intra-acinar pulmon-ary arteries.It is due to both hypertrophy and hyperplasia of smooth musclefibers as well as increase in connective tissue matrix and elasticfibers in the med-ia of muscular arteries.Intimal thickening may be concentric laminar,eccen-tric or concentric non-laminar.Ultrastructurally and im-muno-histochemically the intimal cells show features of fibroblasts,myofibroblasts and smooth muscle cells.Adventitial thickening occurs in most cases of PAH but it is more difficult to evaluate.Complex lesions.The plexiform lesion is a focal prolif-eration of endothelial channels lined by myofibroblasts, smooth muscle cells and connective tissue matrix.These lesions are at an arterial branching point or at the origin of a supernumerary artery,distally to marked oblitera-tive intimal thickening of the parent artery.The fre-quency of the plexiform lesions in PAH remains undetermined.Arteritis may be associated with plexi-form lesions and it is characterised by a necrosis of the arterial wall withfibrinoid insudation and infiltration with inflammatory cells.All the above changes are seen typically in clinical classification(Table1)groups 1.1(IPAH), 1.2(FPAH) and1.3(APAH).Pulmonary occlusive venopathy(also called pulmonary veno-occlusive disease)Pulmonary occlusive venopathy accounts for a relatively small proportion of cases of PH;main histo-pathological features consist of extensive and diffuse occlusion of pul-monary venules and veins of various sizes.The luminal occlusion can be either solid or eccentric.In addition, the media may be thickened.In pulmonary occlusive ven-opathy,large amounts of haemosiderin are found both within the cytoplasm of alveolar macrophages and type II pneumocytes,as well as deposits in the interstitium. The capillary vessels are engorged and prominent and they may be so tortuous as to mimic pulmonary capillary haemangiomatosis.Pulmonary arterioles can show remodelling with medial hypertrophy and intimalfibro-sis.Plexiform lesions andfibrinoid arteritis are not de-scribed in pulmonary occlusive venopathy.The pulmonary interstitium frequently shows oedema inthe 2248ESC Guidelineslobular septa,which may progress to interstitialfibrosis. Lymphatics within the lung and pleura are also dilated. These changes are seen typically in clinical classification (Table1)group1.4.1(PVOD).Pulmonary microvasculopathy(also called pulmonary capillary haemangiomatosis) Pulmonary microvasculopathy is another rare condition characterised by localised capillary proliferation within the lung.The distribution of pulmonary microvasculopa-thy is usually panlobar and patchy.The abnormal prolif-erating capillaries infiltrate the walls of arteries and veins invading muscular walls and occluding the lumen. In the areas of capillary proliferation,pulmonary haemo-siderosis,characterised by haemosiderin-laden macro-phages and type II pneumocytes,is also present. Similar to pulmonary occlusive venopathy,the pulmon-ary arteries in pulmonary microvasculopathy show marked muscular hypertrophy and intimal thickening. These changes are seen typically in clinical classification (Table1)group1.4.2(PCH).Finally,there are unclassifiable conditions with atyp-ical histopathological features or inadequate sampling of blood vessels.Pathogenesis of pulmonary arterial hypertensionThe exact processes that initiate the pathological changes seen in PAH are still unknown even if we now understand more of the mechanisms involved.It is recog-nised that PAH has a multi-factorial pathobiology that in-volves various biochemical pathways and cell types.The increase of PVR is related to different mechanisms including vasoconstriction,obstructive remodelling of the pulmonary vessel wall,inflammation and thrombosis.Pulmonary vasoconstriction is believed to be an early component of the pulmonary hypertensive process.34 Excessive vasoconstriction has been related to abnormal function or expression of potassium channels in the smooth muscle cells35and to endothelial dysfunction.10 Reduced plasma levels of a vasodilator and antiprolifera-tive substance such as Vasoactive Intestinal Peptide has been shown in patients with PAH.36Endothelial dysfunction leads to chronically impaired production of vasodilators such as nitric oxide(NO)and prostacyclin along with overexpression of vasoconstric-tors such as thromboxane A2(TxA2)and endothelin-1 (ET-1).10Many of these abnormalities both elevate vas-cular tone and promote vascular remodelling.The process of pulmonary vascular remodelling in-volves all layers of the vessel wall and is characterised by proliferative and obstructive changes that involve sev-eral cell types including endothelial,smooth muscle and fibroblasts.6,7In addition,in the adventitia there is in-creased production of extracellular matrix including collagen,elastin,fibronectin,and tenascin.37Angiopoie-tin-1,an angiogenic factor essential for vascular lung development,seems to be upregulated in cases of PH correlating directly with the severity of the disease.38 Also inflammatory cells and platelets may play a sig-nificant role in PAH.In fact,inflammatory cells are ubiq-uitous in PAH pathological changes and pro-inflammatory cytokines are elevated in the plasma of PAH patients.39 Alterations in the metabolic pathways of serotonin,a pulmonary vasoconstrictor substance stored in platelets, have also been detected in PAH patients.40Prothrombotic abnormalities have been demonstrated in PAH patients41and thrombi are present in both micro-circulation and elastic pulmonary arteries.6In fact,fibri-nopeptide A levels that reflect thrombin activity,42and TxA2levels,43are both elevated in patients with IPAH.Despite the identification of mutations in the BMPR2 in the majority of cases of familial PAH,8,9the pathobio-logical links between this genetic abnormality and the development of pulmonary vascular hypertensivedisease ESC Guidelines2249have not been clarified.On the other hand,the high fre-quency of‘‘true’’sporadic IPAH cases and reduced pen-etrance of familial PAH(only20%of BMPR2gene mutation carriers manifest the disease),suggests that additional triggers are required for the development of the condition.Mechanisms could be second somatic mutations within an unstable BMPR-2pathway,44poly-morphisms for genes related to PAH[serotonin trans-porter gene(5HTT),40nitric oxide synthase(ec-NOS) gene45and carbamyl-phosphate synthase(CPS)gene46] or any stimulus able to disrupt pulmonary vascular cells growth control.In addition there may be further genes, possibly related to the BMP/TGF-b v pathway,to be iden-tified.Indeed,mutations in the TGF-b v receptors,acti-vin-receptor-like kinase1(ALK-1)and endoglin,have been identified in PAH patients with a personal or family history of hereditary haemorrhagic telangiectasia,i.e. Osler–Weber–Rendu.26,47Even if many pathobiological mechanisms have been identified in the cells and tissues of PAH patients,the ex-act interactions between these mechanisms in initiating and progressing the pathological processes are not well understood.Possible theoretical pathways(Fig.1)in-clude the classical interaction between genetic predispo-sition and risk factors that may induce changes in different cell types(smooth muscle cells,endothelial cells,inflammatory cells,platelets)and in the extracel-lular matrix of pulmonary microcirculation.The imbalance between thrombogenic,mitogenic,proinflam-matory and vasoconstrictive factors as opposed to anticoagulant,antimitotic and vasodilating mechanisms may initiate and perpetuate interacting processes such as vasoconstriction,proliferation,thrombosis and inflammation in the lung microcirculation.These mecha-nisms are responsible for the initiation and progression of pathological obstructive changes typical of PAH.The consequent increase of PVR leads to right ventricular overload and eventually to right ventricular failure and death.Future studies are required tofind which,if any,of these abnormalities initiates PAH and which are best tar-geted to cure the disease.Diagnostic strategyThe diagnostic process of PH requires a series of investi-gations that are intended to make the diagnosis,to clar-ify the clinical class of PH and the type of PAH and to evaluate the functional and haemodynamic impairment. For practical purposes it can be useful to adopt a sequen-tial approach that includes four stages(Fig.2):I.Clinical suspicion of pulmonary hypertensionII.Detection of pulmonary hypertensionIII.Pulmonary hypertension clinical class identification IV.Pulmonary arterial hypertension evaluation(type, functional capacity,haemodynamics)2250ESC Guidelines。
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Distribution of patients with PAH according to age based on sex.
概念
肺高血压（Pulmonary Hypertension）是指任何系统或者局 部病变而引起的肺循环血压增高，包括肺动脉高压，肺静 脉高压，混合性肺高压。
肺动脉高压(Pulmonary Arterial Hypertension)是指孤立的肺 动脉血压增高，肺静脉压力应正常，主要原因是肺小动脉 原发病变而导致的肺动脉阻力增加。
>30mmHg 和肺血管阻力> 3 Wood 对于静息状态下mPAP= 21-24 mm Hg需进一步研究
肺动脉高压: 除了上述肺高压的标准之外，尚需包括肺毛细 血管嵌顿压（PCWP）<15 mmHg
诊断的策略
1）探查可能导致肺血管病变的危险因素； 2）发现有无肺高压的表现； 3）肺高压归类； 4）对怀疑有肺高压表现的患者确诊； 5）决定正确的治疗策略。
特发性肺动脉高压（Idiopathic Pulmonary Arterial Hypertension）是肺动脉高压的一种，指没有发现任何已 知的原因包括遗传，病毒，药物，而发生的肺动脉高压。
2008年Dana point 分类( JACC,in press )
诊断标准
肺高血压:
新的诊断标准是 静息状态下mPAP > 25mm Hg 去掉了既往诊断标准中的运动时肺动脉平均压
内容
肺动脉高压的发展史 流行病学 概念 分类 诊断 治疗
In 1891, the German pathologist Romberg observed that the heart of an individual, suffering from a stricture of the pulmonary arteries due to severe sclerosis, was double the size of a man´s fist. He again named this disease sclerosis of the pulmonary arteries.
流行病学：NIH Registry Data
女性多，女：男=4:1 预后差 家族遗传性 各个年龄段均可发病
Median Survival = 2.8 yrs
1. Abenhaiml. Et al. N Engl J med 1996; 335: 609-16 2. Rich S, et al. Ann Intern med 1987; 107: 216-23
2008年 德国拜耳医药与中华慈善总会共同设立“中 华慈善总会万他维患者援助项目”
2009年 1. 埃他卡林治疗肺动脉高压的Ⅲ期临床研究 2. 波生坦治疗肺动脉高压临床研究
2010年
A Double-Blind, Placebo-Controlled, Dose-Ranging, Parallel Study of the Phosphodiesterase Type 5 Inhibitor Udenafil in the Treatment of Patients with Pulmonary Arterial Hypertension
A PHASE 3, MULTI-CENTER, RANDOMIZED, DOUBLEBLIND, PLACEBOCONTROLLED, SAFETY AND EFFICACY STUDY OF SITAXSENTAN SODIUM IN SUBJECTS WITH PULMONARY ARTERIAL HYPERTENSION
历史
2001年，波生坦美国上市 2002年，皮下曲前列素上市 2003年，威尼斯第三次WHO肺高压会议 2004年，静脉曲前列素上市，iloprost上市 2005年，西地那非 (revatio)上市 2007年，西他生坦和安贝生坦分别上市，TADALAFIL 试
验（美国） 2008年，加州Dana point 第四次WHO 肺高压会议 2008年，EARLY 试验发表
历史
1950s，Primary pulmonary hypertension 1960s, 阿米雷司上市后的肺高压流行 1973年，日内瓦第一届 WHO 肺高压会议 1981年，NIH组织全美注册登记研究 1992年，Flolan 1998年，法国Evian第二次 WHO 肺高压会议 2000年，探索介入治疗CTEPH发表circulation
European Heart Journal (2009) 30, 2493–2537
2007年
“十一五”国家科技支撑计划重大项目 “提高肺动脉高压诊治水平的研究” 1. 伊前列环素治疗肺动脉高压 2. 西地那非治疗肺动脉高压 3. 他汀类药物治疗肺动脉高压
2008年 VADENAFIL试验（中国）
2010年3月1日起，中华慈善总会和拜耳医药对 需要1年以上万他维治疗的患者提供新的援助 措施
流行病学
以前认为，肺动脉高压是发病率低的一种 疾病，2006年法国的注册登记研究结果：肺 动脉高压的发病率约为15/百万人口。
Humbert M, et al. Pulmonary arterial hypertension in France: results from a national registry. Am J Respir Crit Care Med. 2006;173:1023–30.
2009年
ACCF/AHA 2009 Expert Consensus Document on Pulmonary Hypertension
J. Am. Coll. Cardiol. published Mar 30, 2009
Guidelines for the diagnosis and treatment of pulmonary hypertension