专家建议系统性硬化症患者每年筛查肺高压

马德里——一个国际专家小组在欧洲风湿病学大会上表示，对于系统性硬化症患者应该采用经胸部超声心动图检查联合肺功能检查每年进行1次肺动脉高压(PAH)筛查。该专家组同时还呼吁筛查有硬皮病特征的混合型或其他结缔组织病患者。

密歇根大学安娜堡分校硬皮病项目主任Dinesh Khanna医生表示，这是首次针对系统性硬化症患者进行肺动脉高压筛查提出的循证和共识建议。他们希望这些建议能促使结缔组织病患者中PAH更早被发现，从而改善患者结局。他指出，大约有5%~15%的系统性硬化症患者会发生PAH，而一旦发生PAH，30%的患者会在3年内死亡。尽管目前已有治疗系统性硬化症及其他硬皮病范畴的结缔组织病的药物获准上市，但这些治疗对生存率没有显著影响，医生们惟一能做的就是筛查，随后是早期诊断和治疗。

新建议中提到，需行右心导管检查进行PAH评估的指征包括：经胸超声心动图测量的三尖瓣反流速度超过2.8 m/s；三尖瓣反流速度为2.5~2.8 m/s且合并呼吸困难、疲乏、胸痛、头晕、强肺音或外周水肿等PAH的症状或体征；超声心动图检查显示右心房或心室增大，无论患者是否存在三尖瓣反流的症状或体征。在肺功能检查中，进行右心导管检查的关键指征是用力肺活量/肺部一氧化碳弥散量(DLCO)比＞1.6，或DLCO＜60%且并存PAH的症状或体征；或者是，无论满足其中哪项肺部标准，如果患者最近一次血N端前脑钠肽(NT-ProBNP)水平超过正常上限值的2倍，都应进行右心导管检查，而无需考虑症状和体征。另外，无论患者是否存在PAH的症状和体征，只要满足DETECT研究的筛查策略，就应该进行右心导管检查(Ann. Rheum. Dis. 2013 May 18 [doi:10.1036/annrheumdis-2013-203301])。如果患者显现出新的症状或体征，则应每年进行1次经胸超声心动图检查和肺功能检查筛查，必要时提高筛查频率。NT-ProBNP应该在基线时测量，此后，如果出现新的PAH的症状或体征，则应重复测量。对于被诊断为系统性硬化症或其他硬皮病范畴的结缔组织病且病史在3年以上、DLCO＜60%的患者，宜实施全套的DETECT筛查策略。右心导管检查是确诊PAH的强制性检查。对于没有硬皮病样特征的混合型或其他结缔组织病患者无需进行筛查。


Heather Gladue医生

Khanna医生及其合作者在本次大会上的另一项报告中评估了经胸超声心动图检查和肺功能检查筛查PAH患者的效能。他们使用了2项独立研究中的69例患者的数据，这2项研究共纳入347例因疑似PAH而接受评估的系统性硬化症患者。密歇根大学风湿病学研究员Heather Gladue医生报告称，这项新的回顾性分析显示，经胸超声心动图检查联合肺功能检查筛查对正确排除系统性硬化症患者中的PAH的阴性预测准确度为98%。

专家小组提醒道，上述建议不应代替个体化直接评估；建议的成本效益尚未得到评估。除了密歇根大学的代表外，工作组还包括来自加州大学洛杉矶分校、麻省总医院、斯坦福大学等众多名校或医院的成员。

工作组由硬皮病基金会和肺动脉高血压学会提供支持。Khanna医生声称担任多家药企的顾问，其中包括Actelion、拜耳、基因泰克/罗氏、吉利德、默克及DIGNA公司。Gladue医生报告称无相关利益冲突。

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By: MITCHEL L. ZOLER, Cardiology News Digital Network

MADRID – Patients with systemic sclerosis should undergo annual screening for pulmonary arterial hypertension using a combination of transthoracic echocardiography and pulmonary function tests, an international expert panel said.

These are the first evidence- and consensus-based recommendations for pulmonary arterial hypertension (PAH) screening in patients with systemic sclerosis, and the panel also called for screening patients with mixed or other connective tissue diseases with scleroderma features. "Our hope is that these recommendations will lead to earlier detection of PAH in connective tissue diseases and improve patient outcomes," Dr. Dinesh Khanna said while presenting the screening recommendations at the annual European Congress of Rheumatology.

About 5%-15% of patients with systemic sclerosis develop PAH, and once PAH occurs, up to 30% of patients will die within 3 years, said Dr. Khanna, director of the scleroderma program at the University of Michigan, Ann Arbor.

"Despite having approved drugs available" to treat systemic sclerosis and other scleroderma-spectrum disorder connective tissue diseases, these treatments "have not had a huge impact on survival. The only thing we can offer patients is screening, followed by early diagnosis and treatment," Dr. Khanna said in an interview.

The new recommendations say that patients with a tricuspid regurgitant velocity measured by transthoracic echocardiography greater than 2.8 m/s require assessment for PAH by right heart catheterization. Right heart catheterization is also needed for patients with a tricuspid regurgitant velocity of 2.5-2.8 m/s if they also have signs or symptoms of PAH such as dyspnea, fatigue, chest pain, dizziness, loud pulmonary sound, or peripheral edema. Another echo finding that should trigger right heart catheterization regardless of signs or symptoms or tricuspid regurgitation is right atrial or ventricular enlargement.

The key measures on pulmonary function tests that trigger right heart catheterization is a forced vital capacity (FVC) to diffusion capacity of lungs for carbon monoxide (DLCO) ratio of more than 1.6, or a DLCO of less than 60% if either appears in the setting of PAH signs or symptoms. Alternatively, meeting either of these pulmonary criteria should lead to right heart catheterization regardless of signs and symptoms if the patient’s most recent blood level of N-terminal pro-brain natriuretic peptide (NT-ProBNP) was greater than twice the upper limit of normal.

The panel also said that patients should undergo right heart catheterization regardless of PAH signs and symptoms if they fulfill the screening algorithm developed for the DETECT study (Ann. Rheum. Dis. 2013 May 18 [doi:10.1036/annrheumdis-2013-203301]).

The panel recommended annual transthoracic echo and pulmonary function test screening, or more frequently if a patient shows new signs or symptoms. Measurement of NT-ProBNP should happen at baseline, and then be repeated if new signs or symptoms of PAH appear. They also recommended applying the full DETECT screening algorithm in patients diagnosed with systemic sclerosis or other scleroderma spectrum connective-tissue disease for more than 3 years and a DLCO that is less than 60%. Right heart catheterization is mandatory to definitively diagnose PAH, Dr. Khanna stressed. The panel also said screening is not needed in patients with mixed- or other connective tissue disorders who did not have scleroderma-like features.

In a separate report at the meeting Dr. Khanna and his associates assessed the ability of transthoracic echocardiography and pulmonary function tests to screen patients with PAH. They used data from 69 patients with PAH in two separate reported series that together had 347 patients with systemic sclerosis who underwent assessment for suspected PAH (J. Rheumatol. 2011;38:2172-9 and J. Rheumatol. 2010;37:2290-8).

The new, retrospective analysis showed that combining transthoracic echo and pulmonary-function test screens can have a negative predictive accuracy of 98% for correctly ruling out PAH in patients with systemic sclerosis, reported Dr. Heather Gladue, a rheumatology fellow at the University of Michigan.

The recommendations panel cautioned that its proposals should not substitute for individualized, direct assessment of each patient. The panel also noted that the cost effectiveness of its recommendations had not yet been assessed. In addition to representatives from the University of Michigan, the task force included members from the University of California, Los Angeles; Massachusetts General Hospital, Boston; Stanford (Calif.) University; the University of Zurich; University Hospital in Lille, France; the University of Paris-South; McGill University, Montreal; Johns Hopkins University, Baltimore; and St. Joseph Hospital, Phoenix.

The task force was supported by the Scleroderma Foundation and the Pulmonary Hypertension Association. Dr. Khanna said that he has been a consultant to several drug companies including Actelion, Bayer, Genentech/Roche, Gilead, Merck, and DIGNA. Dr. Gladue said that she had no disclosures.