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盘点:肺动脉高压2016研究新进展

2016-09-02 MedSci MedSci原创

肺动脉高压是一种严重危害人类生命健康的疾病,包括动脉性肺动脉高压、左心疾病相关肺动脉高压、肺部疾病或低氧相关肺动脉高压、慢性血栓栓塞性肺动脉高压以及未明机制的肺动脉高压等五大类。其主要特征是肺血管阻力进行性升高,患者由于缺氧导致嘴唇呈现蓝紫色,故称“蓝嘴唇”。如不积极治疗,大部分患者可能会死于右心衰竭,因此该疾病也被称为“心血管系统的恶性肿瘤”。 这里小M盘点了2016年以来关于肺动脉高压的新

肺动脉高压是一种严重危害人类生命健康的疾病,包括动脉性肺动脉高压、左心疾病相关肺动脉高压、肺部疾病或低氧相关肺动脉高压、慢性血栓栓塞性肺动脉高压以及未明机制的肺动脉高压等五大类。其主要特征是肺血管阻力进行性升高,患者由于缺氧导致嘴唇呈现蓝紫色,故称“蓝嘴唇”。如不积极治疗,大部分患者可能会死于右心衰竭,因此该疾病也被称为“心血管系统的恶性肿瘤”。 这里小M盘点了2016年以来关于肺动脉高压的新近研究与大家分享。

【1】利奥西呱治疗慢性血栓栓塞性肺动脉高压的安全性耐受性较好

近期有研究者发现,慢性血栓栓塞性肺动脉高压患者长期使用利奥西呱耐受性好,此外研究人员还发现了两个与治疗相关的预后因素。

研究人员对CHEST-2开放研究中的237名参与者进行了研究,这些患者服用利奥西呱2年,每天3次,最大剂量2.5 mg。研究者分析了患者基线和随访3年的6分钟步行距离(6MWD)、WHO功能分类、N末端脑钠肽激素原(NT-proBNP)浓度,还有生存和临床恶化等情况。

研究者发现,2年后患者的总生存率为 93%,无临床恶化生存率为82%。6MWD和NT-proBNP浓度无论是基线还是2年后,均与总生存率相关,还有从基线到第2年的6MWD变化也与之相关。

此外研究者还发现了基线WHO功能分级与总生存率和临床恶化间的关联。使用利奥西呱的患者其安全性没有显著变化,不过有129名(54%)患者出现了不良事件,其中14名(6%)患者因不良反应停止治疗。(文章详见——Lancet Respir Med:利奥西呱治疗慢性血栓栓塞性肺动脉高压的安全性耐受性研究



【2】肺动脉高压发病机制研究获重大进展

来自美国伊利诺伊大学的研究人员在心血管顶尖杂志《循环》报道了肺动脉高压发生发展的可能病因。肺动脉高压是由多种因素引起肺动脉血管阻力持续性增强,最后导致右心负荷增加和心衰,死亡率极高,目前的治疗手段非常有限。

该研究中,研究人员发现在小鼠的内皮细胞和骨髓细胞上特异性敲除缺氧诱导因子(HIF)的羟化酶(PHD2)能够诱导和人非常相似的肺动脉高压模型,这一研究第一次证明小鼠也能模拟人肺动脉高压的发生发展,进一步拓展了肺高压研究手段。研究者发现PHD2的缺失重现了持续升高的右心舒张压,右心肥大,肺动脉血管重构,包括大小肺血管堵塞和病变等。

接着研究者发现内皮细胞PHD2的缺失是导致肺动脉高压的原因,而骨髓细胞PHD2的缺失是促进肺动脉高压进展的重要因子。进一步利用双基因敲除模型,结果发现PHD2缺失后促进HIF2a的激活(而不是HIF1a),导致肺动脉高压的发生。同时研究人员在自发性肺动脉高压病人的肺病理切片上发现内皮细胞PHD2的缺失表达,进一步明确了PHD2的缺失是导致肺动脉高压的罪魁祸首,该研究为靶向肺动脉高压的治疗提供全新的思路。(文章详见——Circulation:肺动脉高压发病机制研究获重大进展

【3】联合疗法vs.单一疗法治疗肺动脉高压的临床疗效

关于联合靶向疗法与单一疗法治疗肺动脉高血压(PAH)的效果,一些随机对照研究和荟萃分析的结果是相互矛盾的。为此,研究人员采用了系统回顾和荟萃分析来评估PAH特殊疗法与单一疗法对治疗严重PAH患者的效果。

研究人员搜集了MEDLINE、Embase和科克伦图书馆,1990年1月1日至2015年5月31日发表的评估PAH特殊结合疗法与PAH单一疗法治疗患者(年龄超过12岁)的前瞻性随机对照研究(实验至少持续12周)。在搜索的2017项研究中,研究人员选择了17项研究(4095位患者),其中15项研究评估了患者的病情恶化程度。结果表明,相比单一疗法而言,联合疗法能显著降低患者的病情恶化程度。

研究结果表明,相比单一疗法而言,联合疗法治疗PAH更能显著降低病人病情的恶化程度。但是由于实验偏倚的存在,因此研究结果有一定的局限性。且许多采用联合疗法的患者病情也存在恶化,因此研究人员表示仍需进行更进一步的研究。(文章详见——Lancet Respir Med:联合疗法vs.单一疗法治疗肺动脉高压的临床疗效


【4】Riociguat可用于长期治疗慢性血栓栓塞性肺动脉高压


慢性血栓栓塞性肺动脉高压(CTEPH)是一种罕见的,衰弱的和威胁生命的疾病。研究人员调查了在无法手术治疗CTEPH或肺部内膜切除术(PEA)后出现持续性或反复性肺动脉高压的患者中疾病严重程度标志和长期结果之间的关联,这些患者一直接受可溶性苷酸环化酶刺激riociguat治疗。研究人员还从CHEST-2的最后数据中分析了安全性和有效性,在该试验中,大多数患者接受riociguat至少2年。

CHEST-1研究符合条件的患者被纳入CHEST-2这一开放性的延伸研究中,在CHEST-2中,所有患者均接受riociguat,个别调整为最大剂量每天三次2.5毫克。CHEST-2研究共包括237例患者。在2年时,总生存率为93%,无临床恶化生存率为82%。总生存率6MWD和NT-proBNP浓度在基线和在随访过程中都有显著关联。6MWD从基线的变化也显著与生存相关。在基线和随访的WHO的功能分级与总生存率无显著的关联,但与临床无恶化生存期有关。大多数患者对于Riociguat有较好的耐受性,也没有识别到新的安全信号。共有129例(54%)患者发生严重不良事件,14(6%)例患者因为不良事件停止riociguat治疗。(文章详见—— Lancet子刊:Riociguat可用于长期治疗慢性血栓栓塞性肺动脉高压

【5】儿童肺动脉高压患者识别标准的研究

在肺动脉高压(PAH)患者中,急性血管扩张反应试验(AVT)对于使用钙通道阻滞剂(CCB)疗法的成人患者是非常重要的,因为其可以用来确定预后情况。但是,在儿童PAH中,用于识别急性反应和CCB使用的标准还未被充分研究。本研究试图描述儿童PAH患者目前的AVT临床实践和后续的治疗策略。

从2008年1月到2013年5月,529例连续被确诊为肺动脉高压的儿童被招募到一项国际登记中。研究人员分析了那些可评价AVT的儿童。在382例可评估AVT的儿童中,212例有特发性/家族性PAH(IPAH/FPAH),105例PAH与先天性心脏疾病(PAH-CHD)有关。

在70%的患者中,AVT使用吸入一氧化氮进行;其它试剂在其余患者中使用。在IPAH/FPAH患者中,根据医师报告,78例(37%)患者均为急性反应;根据REVEAL儿童标准,62例(30%)患者有急性反应;根据Sitbon标准,32例(15%)有急性反应。对于PAH-CHD患者,AVT应答的数量分别为38(36%),14(13%)和7(7%)例。由治疗医生判断的AVT应答状态和由发表的反应标准判断的之间的相关性较差。此外,由治疗医生判断的急性应答的IPAH/FPAH患者中,只有23%使用了CCB治疗,而没有进行额外的PAH靶向治疗。而Sitbon标准筛选了预后较好的患者,这些患者通过CCB治疗有了较好的结果。

在目前实践中,当前国际准则识别AVT及后续CCB治疗的反应显示出较大的差异。另外,在儿科IPAH患者中,当用CCB治疗时,Sitbon标准能识别具有良好预后的患者。(文章详见——JACC:儿童肺动脉高压患者识别标准的研究


【6】慢性血栓栓塞性肺动脉高压患者,手术治疗的长期预后会更好

慢性血栓栓塞性肺动脉高压(CTEPH),是一种罕见的急性肺栓塞并发症,特点是较大肺动脉的血栓栓塞联合小血管病变。它可以通过肺部动脉内膜切除术治愈,不能动手术的病人可以通过药物治疗在临床上改善。

该研究招募了679例新诊断的CTEPH患者,在手术患者(n=404)中,1,2和3年的估计生存率分别为93%, 91%, 和89%;而非手术患者中(n=275),生存率仅为88%, 79%, 和70%。在两组患者中,PAH靶向治疗不会显著影响生存率。手术患者和非手术患者的死亡率都与NYHA心功能分级IV,右心房压力增加,和癌症病史相关。其他相关的死亡率与PAH靶向药物、术后pH值、手术并发症和手术患者的额外的心脏手术,合并症例如冠状动脉疾病、左心衰竭、以及未手术患者的COPD相关。

总而言之,该研究发现手术患者的长期预后到现在为止是可以接受的,并且比非手术患者的预后要更好。(文章详见——Circulation:慢性血栓栓塞性肺动脉高压(CTEPH)患者,手术治疗的长期预后会更好



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    2016-09-06 1e0d99ddm02(暂无匿称)

    学习了,分享一下!

    0

  3. 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    2016-09-06 1e0d99ddm02(暂无匿称)

    学习了,分享一下!

    0

  4. 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authenticateStatus=null, createdAvatar=https://cdnapi.center.medsci.cn/medsci/head/2017/11/23/ac01daf0962458a9eb8c0b1e2f6ce5bc.jpg, createdBy=04b81710322, createdName=1771ae4158m, createdTime=Sun Sep 04 09:20:00 CST 2016, time=2016-09-04, status=1, ipAttribution=)]
    2016-09-06 1e0d99ddm02(暂无匿称)

    赞一个!!

    0

  5. 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    2016-09-06 1e0d99ddm02(暂无匿称)

    基层医院一般一遇见肺栓塞就直接转院了!

    0

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    2016-09-04 ylzr123

    赞!好文章,拜读,值得深入学习!

    0

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    2016-09-04 有备才能无患

    这么多新药,基层医院只能是改善缺氧,缓解肺动脉高压,必要时用钙离子拮抗剂

    0

  8. 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    2016-09-04 1771ae4158m

    学习了,好

    0

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    2016-09-04 1771ae4158m

    学习一下,有意思

    0

  10. 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    2016-09-04 1771ae4158m

    学习一下,有意思

    0

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