今日の臨床サポート

慢性血栓塞栓性肺高血圧症

著者: 田邉信宏 千葉県済生会習志野病院 肺高血圧症センター

監修: 久保惠嗣 信州大学名誉教授

著者校正/監修レビュー済:2022/07/06
参考ガイドライン:
  1. 日本肺高血圧・肺循環学会慢性血栓塞栓性肺高血圧症(CTEPH)診療ガイドライン 2022(2022年5月閲覧)
  1. 日本循環器学会肺高血圧症治療ガイドライン(2017年改訂版)(2022年4月閲覧)
  1. Konstantinides SV, Meyer G, Becattini C, Bueno H, Geersing G-J, Harjola V-P, Huisman MV, Humbert M, Jennings CS, Jimenez D, Kucher N, Lang IM, Lankeit M, Lorusso R, Mazzolai L, Meneveau N, Ní Áinle F, Prandoni P, Pruszczyk P, Righini M, Torbicki A, Van Belle E, Zamorano JL, ESC Scientific Document Group. 2019 ESC Guidelines for the diagnosis and management of acute pulmonary embolism developed in collaboration with the European Respiratory Society (ERS). Eur Heart J 2020; 41: 543–603.
  1. Delcroix M, Torbicki A, Gopalan D, Sitbon O, Klok FA, Lang I, Jenkins D, Kim NH, Humbert M, Jais X, Vonk Noordegraaf A, Pepke-Zaba J, Brénot P, Dorfmuller P, Fadel E, Ghofrani HA, Hoeper MM, Jansa P, Madani M, Matsubara H, Ogo T, Grünig E, D'Armini A, Galie N, Meyer B, Corkery P, Meszaros G, Mayer E, Simonneau G. ERS statement on chronic thromboembolic pulmonary hypertension Eur Respir J. 2021 Jun 17;57(6):2002828. doi: 10.1183/13993003.02828-2020. Print 2021 Jun.PMID: 33334946
患者向け説明資料

概要・推奨   

  1. 原因不明の労作時の息切れを呈する患者では、慢性血栓塞栓性肺高血圧症(CTEPH)を疑うことが重要である(推奨度1)
  1. CTEPH発症の予測のため、急性血栓肺塞栓症後3-6ケ月後に臨床的評価をすることが有用である(推奨度1)
  1. 肺換気・血流スキャンは、CTEPH診断において、胸部造影CTより特異度、敏感度ともに高く、肺血流スキャンが正常の場合、本症は否定される(推奨度1)
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(詳細はこちらを参照)
著者のCOI(Conflicts of Interest)開示:
田邉信宏 : 講演料(ヤンセンファーマ,バイエル薬品,日本新薬)[2022年]
監修:久保惠嗣 : 特に申告事項無し[2022年]

改訂のポイント:
  1. 慢性血栓塞栓性肺高血圧症発症予測のため、急性肺塞栓症後3−6ケ月に臨床的評価を行うことを明記。
  1. バルーン肺動脈拡張術の海外での普及、ガイドライン記載に基づきエビンデンスランクを変更。
  1. セレキシパグを用いた慢性血栓塞栓性肺高血圧症の無作為化比較試験の結果および適用追加。

病態・疫学・診察

疾患情報(疫学・病態)  
  1. CTEPHは、器質化した血栓により肺動脈が慢性的に閉塞を起こし、肺高血圧症を合併するもので、労作時の息切れが特徴である。
  1. CTEPHは、指定難病であり、Stage2以上を認める場合などでは申請し認定されると保険料の自己負担分の一部が公費負担として助成される([平成27年1月施行])。2020年度末で4,608人の患者が存在する[1]
  1.  難病法に基づく医療費助成制度 
  1. 肺動脈性肺高血圧症との鑑別には、肺換気・血流スキャンが有用で、本症では換気に異常を認めない区域性の血流欠損を呈する。
  1. 確定診断は、胸部造影CTあるいは肺動脈造影の慢性血栓所見と、右心カテーテル検査で、肺動脈楔入圧が正常な肺高血圧症を確認することによる(認定基準の表)[2]
 
CTEPHの診断基準

本症は、厚生労働省の特定疾患、治療給付対象疾患であり、表の認定基準を満たすものとされる。

 
  1. 肺高血圧症の重症な例では内科的治療には限界があり、予後不良とされてきたが、PEA(<図表>)によりQOLや生命予後の改善が得られる症例が存在する。
 
PEAによって、摘出された血栓内膜標本

内弾性板のところで、剝離面をみつけ、血栓を内膜とともに鋳型状に摘出する。

出典

img1:  著者提供
 
 
 
PEAによって、摘出された血栓内膜標本 

内弾性板のところで、剝離面をみつけ、血栓を内膜とともに鋳型状に摘出する。
術前 平均肺動脈圧70 mmHg、肺血管抵抗1,699 dyn・s・cm-5であったが、術後 平均肺動脈圧16 mmHg、肺血管抵抗183 dyn・s・cm-5まで改善した。

出典

img1:  著者提供
 
 
 
  1. BPAによって、肺血行動態、予後の改善が得られるため、手術の適応とならない例では、熟練した医師によるBPAを考慮する。
問診・診察のポイント  
  1. 労作時の息切れを主訴とする患者では、本症を疑うことが最も重要である[2][3]
  1. 呼吸器疾患患者で、肺機能低下に比して息切れが強い場合も、本症を疑う。

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文献 

A Palla, B Formichi, A Santolicandro, G Di Ricco, C Giuntini
From not detected pulmonary embolism to diagnosis of chronic thromboembolic pulmonary hypertension: a retrospective study.
Respiration. 1993;60(1):9-14.
Abstract/Text The past and present clinical history of 13 patients with hemodynamic and angiographic diagnosis of chronic thromboembolic pulmonary hypertension (CTPH) was reviewed in order to investigate the reasons for failure of resolution of acute pulmonary embolism (PE) and findings useful for diagnosis of CTPH. All patients had chest radiograph, ECG, arterial blood gas analysis and pulmonary perfusion scintigraphy performed. Clinical assessment demonstrated that no patient had diagnosis and treatment of the several retrospectively identified episodes of PE (from 1 to 8); the lack of diagnosis was due to underestimation of symptoms and signs such as dyspnea (85%), pleuritic chest pain (31%) or phlebitis (46%) that were present months or years earlier. Alternative diagnoses erroneously made were dyspnea of unknown origin (5 cases), left heart failure (4 instances) and pneumonia (2 cases). Once CTPH has developed, chronic dyspnea (92%) and substernal chest pain (100%) are almost always present: chest radiograph and ECG show signs of chronic hypertension such as enlargement of hila (100%), right heart sections (77%), azygos vein (46%) and P pulmonale (67%), T inversion on right precordial leads (75%), S-T segment depression (75%), respectively. Perfusion scintigraphy shows severe perfusion impairment (55.7% of the total vascular bed) paralleled by severe hypoxia (standard PaO2 = 49 +/- 14.1 mm Hg). In conclusion, patients with PE who develop CTPH are not diagnosed and thus untreated because clinical symptoms and signs of acute PE have not been recognized. If CTPH develops, clinical assessment (including simple and noninvasive techniques such as chest radiograph, ECG and blood gas analysis) may show a quite characteristic pattern useful for diagnosis.

PMID 8469823
Michael R Jaff, M Sean McMurtry, Stephen L Archer, Mary Cushman, Neil Goldenberg, Samuel Z Goldhaber, J Stephen Jenkins, Jeffrey A Kline, Andrew D Michaels, Patricia Thistlethwaite, Suresh Vedantham, R James White, Brenda K Zierler, American Heart Association Council on Cardiopulmonary, Critical Care, Perioperative and Resuscitation, American Heart Association Council on Peripheral Vascular Disease, American Heart Association Council on Arteriosclerosis, Thrombosis and Vascular Biology
Management of massive and submassive pulmonary embolism, iliofemoral deep vein thrombosis, and chronic thromboembolic pulmonary hypertension: a scientific statement from the American Heart Association.
Circulation. 2011 Apr 26;123(16):1788-830. doi: 10.1161/CIR.0b013e318214914f. Epub 2011 Mar 21.
Abstract/Text Venous thromboembolism (VTE) is responsible for the hospitalization of >250 000 Americans annually and represents a significant risk for morbidity and mortality. Despite the publication of evidence-based clinical practice guidelines to aid in the management of VTE in its acute and chronic forms, the clinician is frequently confronted with manifestations of VTE for which data are sparse and optimal management is unclear. In particular, the optimal use of advanced therapies for acute VTE, including thrombolysis and catheter-based therapies, remains uncertain. This report addresses the management of massive and submassive pulmonary embolism (PE), iliofemoral deep vein thrombosis (IFDVT),and chronic thromboembolic pulmonary hypertension (CTEPH). The goal is to provide practical advice to enable the busy clinician to optimize the management of patients with these severe manifestations of VTE. Although this document makes recommendations for management, optimal medical decisions must incorporate other factors, including patient wishes, quality of life, and life expectancy based on age and comorbidities. The appropriateness of these recommendations for a specific patient may vary depending on these factors and will be best judged by the bedside clinician.

PMID 21422387
A Ribeiro, P Lindmarker, H Johnsson, A Juhlin-Dannfelt, L Jorfeldt
Pulmonary embolism: one-year follow-up with echocardiography doppler and five-year survival analysis.
Circulation. 1999 Mar 16;99(10):1325-30.
Abstract/Text BACKGROUND: The long-term prognosis for patients with pulmonary embolism (PE) is dependent on the underlying disease, degree of pulmonary hypertension (PH), and degree of right ventricular (RV) dysfunction. A precise description of the time course of pulmonary artery pressure (PAsP)/RV function is therefore of importance for the early identification of persistent PH/RV dysfunction in patients treated for acute PE. Other objectives were to identify variables associated with persistent PH/RV dysfunction and to analyze the 5-year survival rate for patients alive 1 month after inclusion.
METHODS AND RESULTS: Echocardiography Doppler was performed in 78 patients with acute PE at the time of diagnosis and repeatedly during the next year. A 5-year survival analysis was made. The PAsP decreased exponentially until the beginning of a stable phase, which was 50 mm Hg at the time of diagnosis of acute PE was associated with persistent PH after 1 year. The 5-year mortality rate was associated with underlying disease. Only patients with persistent PH in the stable phase required pulmonary thromboendarterectomy within 5 years.
CONCLUSIONS: An echocardiography Doppler investigation performed 6 weeks after diagnosis of acute PE can identify patients with persistent PH/RV dysfunction and may be of value in planning the follow-up and care of these patients.

PMID 10077516
Marion Delcroix, Adam Torbicki, Deepa Gopalan, Olivier Sitbon, Frederikus A Klok, Irene Lang, David Jenkins, Nick H Kim, Marc Humbert, Xavier Jais, Anton Vonk Noordegraaf, Joanna Pepke-Zaba, Philippe Brénot, Peter Dorfmuller, Elie Fadel, Hossein-Ardeschir Ghofrani, Marius M Hoeper, Pavel Jansa, Michael Madani, Hiromi Matsubara, Takeshi Ogo, Ekkehard Grünig, Andrea D'Armini, Nazzareno Galie, Bernhard Meyer, Patrick Corkery, Gergely Meszaros, Eckhard Mayer, Gérald Simonneau
ERS statement on chronic thromboembolic pulmonary hypertension.
Eur Respir J. 2021 Jun;57(6). doi: 10.1183/13993003.02828-2020. Epub 2021 Jun 17.
Abstract/Text Chronic thromboembolic pulmonary hypertension (CTEPH) is a rare complication of acute pulmonary embolism, either symptomatic or not. The occlusion of proximal pulmonary arteries by fibrotic intravascular material, in combination with a secondary microvasculopathy of vessels <500 µm, leads to increased pulmonary vascular resistance and progressive right heart failure. The mechanism responsible for the transformation of red clots into fibrotic material remnants has not yet been elucidated. In patients with pulmonary hypertension, the diagnosis is suspected when a ventilation/perfusion lung scan shows mismatched perfusion defects, and confirmed by right heart catheterisation and vascular imaging. Today, in addition to lifelong anticoagulation, treatment modalities include surgery, angioplasty and medical treatment according to the localisation and characteristics of the lesions.This statement outlines a review of the literature and current practice concerning diagnosis and management of CTEPH. It covers the definitions, diagnosis, epidemiology, follow-up after acute pulmonary embolism, pathophysiology, treatment by pulmonary endarterectomy, balloon pulmonary angioplasty, drugs and their combination, rehabilitation and new lines of research in CTEPH.It represents the first collaboration of the European Respiratory Society, the International CTEPH Association and the European Reference Network-Lung in the pulmonary hypertension domain. The statement summarises current knowledge, but does not make formal recommendations for clinical practice.

Copyright ©ERS 2021. For reproduction rights and permissions contact permissions@ersnet.org.
PMID 33334946
Nazzareno Galiè, Marc Humbert, Jean-Luc Vachiery, Simon Gibbs, Irene Lang, Adam Torbicki, Gérald Simonneau, Andrew Peacock, Anton Vonk Noordegraaf, Maurice Beghetti, Ardeschir Ghofrani, Miguel Angel Gomez Sanchez, Georg Hansmann, Walter Klepetko, Patrizio Lancellotti, Marco Matucci, Theresa McDonagh, Luc A Pierard, Pedro T Trindade, Maurizio Zompatori, Marius Hoeper, Victor Aboyans, Antonio Vaz Carneiro, Stephan Achenbach, Stefan Agewall, Yannick Allanore, Riccardo Asteggiano, Luigi Paolo Badano, Joan Albert Barberà, Hélène Bouvaist, Héctor Bueno, Robert A Byrne, Scipione Carerj, Graça Castro, Çetin Erol, Volkmar Falk, Christian Funck-Brentano, Matthias Gorenflo, John Granton, Bernard Iung, David G Kiely, Paulus Kirchhof, Barbro Kjellstrom, Ulf Landmesser, John Lekakis, Christos Lionis, Gregory Y H Lip, Stylianos E Orfanos, Myung H Park, Massimo F Piepoli, Piotr Ponikowski, Marie-Pierre Revel, David Rigau, Stephan Rosenkranz, Heinz Völler, Jose Luis Zamorano
2015 ESC/ERS Guidelines for the diagnosis and treatment of pulmonary hypertension: The Joint Task Force for the Diagnosis and Treatment of Pulmonary Hypertension of the European Society of Cardiology (ESC) and the European Respiratory Society (ERS): Endorsed by: Association for European Paediatric and Congenital Cardiology (AEPC), International Society for Heart and Lung Transplantation (ISHLT).
Eur Heart J. 2016 Jan 1;37(1):67-119. doi: 10.1093/eurheartj/ehv317. Epub 2015 Aug 29.
Abstract/Text
PMID 26320113
Marius M Hoeper, Joan Albert Barberà, Richard N Channick, Paul M Hassoun, Irene M Lang, Alessandra Manes, Fernando J Martinez, Robert Naeije, Horst Olschewski, Joanna Pepke-Zaba, Margaret M Redfield, Ivan M Robbins, Rogério Souza, Adam Torbicki, Michael McGoon
Diagnosis, assessment, and treatment of non-pulmonary arterial hypertension pulmonary hypertension.
J Am Coll Cardiol. 2009 Jun 30;54(1 Suppl):S85-96. doi: 10.1016/j.jacc.2009.04.008.
Abstract/Text The 4th World Symposium on Pulmonary Hypertension was the first international meeting to focus not only on pulmonary arterial hypertension (PAH) but also on the so-called non-PAH forms of pulmonary hypertension (PH). The term "non-PAH PH" summarizes those forms of PH that are found in groups 2 to 5 of the current classification of PH, that is, those forms associated with left heart disease, chronic lung disease, recurrent venous thromboembolism, and other diseases. Many of these forms of PH are much more common than PAH, but all of them have been less well studied, especially in terms of medical therapy. The working group on non-PAH PH focused mainly on 4 conditions: chronic obstructive lung disease, interstitial lung disease, chronic thromboembolic PH, and left heart disease. The medical literature regarding the role of PH in these diseases was reviewed, and recommendations regarding diagnosis and treatment of PH in these conditions are provided. Given the lack of robust clinical trials addressing PH in any of these conditions, it is important to conduct further studies to establish the role of medical therapy in non-PAH PH.

PMID 19555862
Nina Tunariu, Simon J R Gibbs, Zarni Win, Wendy Gin-Sing, Alison Graham, Philip Gishen, Adil Al-Nahhas
Ventilation-perfusion scintigraphy is more sensitive than multidetector CTPA in detecting chronic thromboembolic pulmonary disease as a treatable cause of pulmonary hypertension.
J Nucl Med. 2007 May;48(5):680-4. doi: 10.2967/jnumed.106.039438.
Abstract/Text UNLABELLED: Pulmonary hypertension (PH) is a progressive disease with a poor prognosis. Identifying chronic thromboembolic pulmonary disease as a cause of PH has major clinical implications as these patients could be potentially offered a surgical cure. Ventilation-perfusion (V/Q) scintigraphy has a high sensitivity to detect embolic disease but its value has been challenged with the emergence of multidetector CT pulmonary angiography (CTPA). We compared the value of V/Q scintigraphy with CTPA in detecting chronic thromboembolic pulmonary disease.
METHODS: We retrospectively reviewed the results of V/Q scintigraphy and CTPA performed on patients who had been referred to the Pulmonary Hypertension Service at Hammersmith Hospital between 2000 and 2005. A total of 227 patients (85 males, 142 females; age range, 18-81 y; mean age, 42 y) had all tests done at Hammersmith Hospital and were included in the study. Interpretation of scans was according to the modified PIOPED (Prospective Investigation of Pulmonary Embolism Diagnosis) criteria. CTPA was considered as suggestive of chronic thromboembolic pulmonary disease if it showed visualization of the thrombus or webs, recanalization, perfusion abnormalities, stenosis, or strictures. Standard pulmonary angiography was performed via femoral approach. In 90% of the cases, CTPA and V/Q scintigraphy were performed within 10 d.
RESULTS: Seventy-eight patients (group A) had a final diagnosis of chronic thromboembolic pulmonary hypertension (CTEPH) and 149 (group B) had non-CTEPH etiology. Among group A, V/Q scintigraphy was reported as high probability in 75 patients, intermediate probability in 1 patient, and low probability in 2 patients. CTPA was positive in 40 patients and negative in 38 patients. Among group B, V/Q scintigraphy was reported as low probability in 134, intermediate probability in 7, and high probability in 8 patients. CTPA was negative in 148 patients and false-positive in 1 patient. Statistical analysis showed V/Q scintigraphy to have a sensitivity of 96%-97.4% and a specificity of 90%-95%. CTPA showed a sensitivity of 51% and a specificity of 99%.
CONCLUSION: Our results demonstrate that V/Q scintigraphy has a higher sensitivity than CTPA in detecting CTEPH as a potential curable cause of PH.

PMID 17475953
Abstract/Text Seventy-six patients with various forms of pulmonary thromboembolic disease were followed-up for 1 to 15 years. All were free of other cardiopulmonary disease at the time of the first examination which was performed at least two months after the last pulmonary embolism. Catheterization was repeated in all survivors on average 4.8 years later. Severe chronic pulmonary hypertension (mean pulmonary artery pressure (PPA greater than 30 mm Hg) did not occur after a single episode of acute embolism, was infrequent after single subacute or recurrent emboli (8 of 9 patients), and was common after occult emboli (12 of 13 patients). Mortality in all clinical groups correlated with PPA and with the presence of right heart failure. In survivors, no correlation was found between the longterm changes of PPA and age, duration of disease, interval between catheterizations, PaO2, or cardiac output. Pulmonary hypertension progressed further in patients with initial PPA greater than 30 mm Hg. In contrast, none of the patients with normal or borderline PPA at the initial examination developed severe pulmonary hypertension during the follow-up. Since the future course of patients could be predicted from the first examination, repeated hemodynamic investigation proved to be of minor prognostic value.

PMID 7056079
Robin Condliffe, David G Kiely, J Simon R Gibbs, Paul A Corris, Andrew J Peacock, David P Jenkins, Denise Hodgkins, Kim Goldsmith, Rodney J Hughes, Karen Sheares, Steven S L Tsui, Iain J Armstrong, Chantal Torpy, Rachel Crackett, Christopher M Carlin, Clare Das, J Gerry Coghlan, Joanna Pepke-Zaba
Improved outcomes in medically and surgically treated chronic thromboembolic pulmonary hypertension.
Am J Respir Crit Care Med. 2008 May 15;177(10):1122-7. doi: 10.1164/rccm.200712-1841OC. Epub 2008 Feb 21.
Abstract/Text RATIONALE: The management of chronic thromboembolic pulmonary hypertension (CTEPH) has changed over recent years with the growth of pulmonary endarterectomy surgery and the availability of disease-modifying therapies.
OBJECTIVES: To investigate the prognosis of CTEPH in a national setting during recent years.
METHODS: All incident cases diagnosed in one of the five pulmonary hypertension centers in the United Kingdom between January 2001 and June 2006 were identified prospectively. Information regarding baseline characteristics, treatment, and follow-up was subsequently collected from hospital records.
MEASUREMENTS AND MAIN RESULTS: A total of 469 patients received a diagnosis, of whom 148 (32%) had distal, nonsurgical disease. One- and three-year survival from diagnosis was 82 and 70% for patients with nonsurgical disease and 88 and 76% for those treated surgically (P = 0.023). Initial functional improvement in patients with nonsurgical disease was noted but did not persist at 2 years. Significant functional and hemodynamic improvements were seen in surgically treated patients with an increase in six-minute-walk distance of 105 m (P < 0.001) at 3 months. Five-year survival from surgery in the 35% of patients who survived to 3 months but had persistent pulmonary hypertension was 94%.
CONCLUSIONS: The prognosis in nonsurgical disease has improved. We have confirmed the previously described good outcome in surgically treated disease. However, we have also demonstrated that the long-term prognosis for patients who have persistent pulmonary hypertension at 3 months after surgery is good. The observed improvements in outcome during the modern treatment era reinforce the importance of identifying patients with this increasingly treatable condition.

PMID 18292468
Rintaro Nishimura, Nobuhiro Tanabe, Toshihiko Sugiura, Ayako Shigeta, Takayuki Jujo, Ayumi Sekine, Seiichiro Sakao, Yasunori Kasahara, Koichiro Tatsumi
Improved survival in medically treated chronic thromboembolic pulmonary hypertension.
Circ J. 2013;77(8):2110-7. Epub 2013 Apr 25.
Abstract/Text BACKGROUND: The surgical indication for chronic thromboembolic pulmonary hypertension (CTEPH) has been modified due to recognition of peripheral type CTEPH and changes in surgical methods and skill. Bosentan and sildenafil are used as modern oral therapy (mod Tx) in patients with inoperable CTEPH, although it remains unknown whether they have positive effects on survival.
METHODS AND RESULTS: A total of 202 patients were diagnosed with CTEPH at Chiba University Hospital between 1986 and 2010, 100 of whom underwent pulmonary endarterectomy. Seven medically treated patients with pulmonary vascular resistance (PVR) ≤ 300 dyn·s·cm(-5) were regarded as having mild disease. Survival rate was stratified by date of diagnosis (group 1, 1986-1998; group 2, 1999-2004; group 3, 2005-2010), and prognostic factors in the remaining 95 medically treated patients were investigated. Group 3 included the most patients treated with mod Tx (group 1, 9.1%; group 2, 24.2%; group 3, 65.0%) and had significantly better survival than either group 1 or 2 (5-year survival: group 1, 54.6%; group 2, 69.7%; group 3, 87.3%). Patients receiving mod Tx had significantly better survival than those not on mod Tx (5-year survival: 88.9% vs. 60.2%). Multivariate analysis showed that mod Tx, lower PVR, and lack of comorbidity were significant predictors of better outcome.
CONCLUSIONS: Medically treated patients with CTEPH had a better survival rate, and the use of mod Tx contributed to improved survival.

PMID 23615047
Keiichi Ishida, Masahisa Masuda, Nobuhiro Tanabe, Goro Matsumiya, Koichiro Tatsumi, Nobuyuki Nakajima
Long-term outcome after pulmonary endarterectomy for chronic thromboembolic pulmonary hypertension.
J Thorac Cardiovasc Surg. 2012 Aug;144(2):321-6. doi: 10.1016/j.jtcvs.2011.09.004. Epub 2011 Oct 10.
Abstract/Text OBJECTIVES: Pulmonary endarterectomy is the treatment of choice for chronic thromboembolic pulmonary hypertension. Although several reports demonstrated excellent medium-term survival after pulmonary endarterectomy, long-term outcomes remain unclear. We reviewed long-term outcomes and determined risk factors for early and late adverse events.
METHODS: Seventy-seven patients were studied. Mean pulmonary arterial pressure was 47±10 mm Hg and pulmonary vascular resistance was 868±319 dyne·s·cm(-5). Disease was classified as chronic thromboembolic pulmonary hypertension type 1 (n=61), type 2 (n=12), or type 3 (n=4). Median and maximum follow-up periods were 5.6 and 20 years, respectively.
RESULTS: There were 11 in-hospital deaths. Nonsurvivors had significantly higher mean pulmonary arterial pressure and pulmonary vascular resistance than did survivors (54±10 vs 46±10 mm Hg; P=.02; 1124±303 vs 824±303 dyne·s·cm(-5); P<.01). In multivariate analysis, preoperative pulmonary vascular resistance was associated with in-hospital death (odds ratio, 1.003; 95% confidence interval, 1.001-1.005; P<.01). During follow-up, there were 10 all-cause deaths, including 5 related to chronic thromboembolic pulmonary hypertension. Freedom from adverse events, including disease-specific death or New York Heart Association functional class III, was 70% at 10 years. In the Cox proportional hazard model, postoperative mean pulmonary arterial pressure was associated with adverse events (hazard ratio, 1.12; 95% confidence interval, 1.03-1.21; P<.01). Receiver operating characteristic curve analysis showed mean pulmonary arterial pressure of 34 mm Hg as cutoff for adverse events.
CONCLUSIONS: Pulmonary endarterectomy had sustained favorable effects on long-term survival. High pulmonary vascular resistance was associated with in-hospital death, and postoperative mean pulmonary arterial pressure was an independent predictor of adverse events.

Copyright © 2012 The American Association for Thoracic Surgery. Published by Mosby, Inc. All rights reserved.
PMID 21992851
Aiko Ogawa, Toru Satoh, Tetsuya Fukuda, Koichiro Sugimura, Yoshihiro Fukumoto, Noriaki Emoto, Norikazu Yamada, Atsushi Yao, Motomi Ando, Hitoshi Ogino, Nobuhiro Tanabe, Ichizo Tsujino, Masayuki Hanaoka, Kenji Minatoya, Hiroshi Ito, Hiromi Matsubara
Balloon Pulmonary Angioplasty for Chronic Thromboembolic Pulmonary Hypertension: Results of a Multicenter Registry.
Circ Cardiovasc Qual Outcomes. 2017 Nov;10(11). doi: 10.1161/CIRCOUTCOMES.117.004029.
Abstract/Text BACKGROUND: Balloon pulmonary angioplasty (BPA) is an alternative therapy for patients with chronic thromboembolic pulmonary hypertension who are ineligible for pulmonary endarterectomy-the standard therapy. Currently, most reported results of BPA are from relatively small cohorts treated at single centers. The present study evaluated the safety and efficacy of BPA for chronic thromboembolic pulmonary hypertension based on a multicenter registry.
METHODS AND RESULTS: A total of 308 patients (62 men and 246 women; mean age, 61 years) underwent 1408 procedures at 7 institutions in Japan. Data were retrospectively reviewed to evaluate clinical outcome and complications. Hemodynamics were significantly improved in 249 patients in whom BPA was terminated, most often because of improvement in mean pulmonary arterial pressure or symptomatic improvement after 1154 procedures. In 196 patients who underwent follow-up right heart catheterization, improvement of hemodynamic parameters was maintained. Mean pulmonary arterial pressure decreased from 43.2±11.0 to 24.3±6.4 mm Hg after final BPA and 22.5±5.4 mm Hg at follow-up, with significant reduction of concomitant use of pulmonary hypertension-targeted therapy and oxygen supplementation. Complications occurred in 511 (36.3%), including pulmonary injury (17.8%), hemoptysis (14.0%), and pulmonary artery perforation (2.9%). Twelve patients (3.9%) died during follow-up, including 8 patients who died within 30 days after BPA. The leading causes of death were right heart failure, multiorgan failure, and sepsis. Overall survival was 96.8% (95% confidence interval, 93.7%-98.4%) at 1 and 2 years and 94.5% (95% confidence interval, 89.3%-97.3%) at 3 years, respectively, after the initial BPA procedure for all 308 patients.
CONCLUSIONS: This multicenter registry suggested improved hemodynamic results after BPA. Complication rates were high, but overall survival was comparable with pulmonary endarterectomy. BPA may be an important therapeutic option in patients with chronic thromboembolic pulmonary hypertension.

© 2017 American Heart Association, Inc.
PMID 29101270
Sert Sena, Mutlu Bulent, Kocakaya Derya, Kaptan Deniz, Ataş Halil, Erdogan Okan, Yıldızeli Bedrettin
Real-life data of direct anticoagulant use, bleeding risk and venous thromboembolism recurrence in chronic thromboembolic pulmonary hypertension patients: an observational retrospective study.
Pulm Circ. 2020 Jan-Mar;10(1):2045894019873545. doi: 10.1177/2045894019873545. Epub 2020 Feb 19.
Abstract/Text Introduction: Lifelong anticoagulation is the cornerstone of the chronic thromboembolic pulmonary hypertension (CTEPH) treatment regardless of the additional pulmonary endarterectomy, balloon pulmonary angioplasty, or medical treatment alone. Aim of this study was to evaluate the rate of oral anticoagulant preferences and document direct oral anticoagulants' (DOACs') safety, efficacy in the CTEPH population.
Methods: Patients' demographic data obtained from database between September 2011 and April 2018. In-hospital events, death, venous thromboembolism (VTE) recurrence, bleeding events and anticoagulant therapy transition were recorded.
Results: We reviewed 501 CTEPH patients who observed 9.0 ± 8.5 years. All-cause death, all bleeding, recurrent VTE was observed in 15.6%, 31% and 12%. Forty-one patients (8.2%) were diagnosed as inoperable. Of all, 15.2% of operable patients remained as residual. All-cause mortality rates were 13.8% (57 pts.) in the warfarin group as compared with 9.7% (13 pts.) in rivaroxaban group (HR: 1.61, 95% CI, 0.89-2.99; p: 0.11). Higher bleeding events occurred with warfarin group (27.1%) as compared with rivaroxaban (24.6%; HR: 1.28, 95% CI, 0.86-1.88; p: 0.22). Major bleeding was significantly higher with warfarin group (HR: 1.94, 95% CI, 1.05-3.62; p: 0.03). Subgroup analysis of all-cause death revealed that this significance dominated by the rate of death according to bleeding events; warfarin versus those seen with rivaroxaban (4.85% vs. 2.2%; HR: 4.75, 95% CI: 1.12-20.16; p = 0.03). The rate of recurrent VTE was found 8.9% in the rivaroxaban group, 10.9% in warfarin group (HR: 1.21, 95% CI, 0.64-2.23; p: 0.55).
Conclusion: DOACs could be a safe and effective alternative for lifelong anticoagulant therapy in CTEPH patients. Rivaroxaban produced similar rates of thromboembolism and non-relevant bleeding compared to those associated with warfarin. The main difference was found with major bleeding that it was mainly associated with the death rate according to major bleeding. Using DOACs might be a more reasonable way to prevent bleeding events without increasing thromboembolic risk.

© The Author(s) 2020.
PMID 32128155
Katherine Bunclark, Michael Newnham, Yi-Da Chiu, Alessandro Ruggiero, Sofia S Villar, John E Cannon, Gerry Coghlan, Paul A Corris, Luke Howard, David Jenkins, Martin Johnson, David G Kiely, Choo Ng, Nicholas Screaton, Karen Sheares, Dolores Taboada, Steven Tsui, Stephen John Wort, Joanna Pepke-Zaba, Mark Toshner
A multicenter study of anticoagulation in operable chronic thromboembolic pulmonary hypertension.
J Thromb Haemost. 2020 Jan;18(1):114-122. doi: 10.1111/jth.14649. Epub 2019 Oct 18.
Abstract/Text BACKGROUND: Chronic thromboembolic pulmonary hypertension (CTEPH) is an uncommon complication of acute pulmonary emboli necessitating lifelong anticoagulation. Despite this, few data exist on the safety and efficacy of vitamin K antagonists (VKAs) in CTEPH and none for direct oral anticoagulants (DOACs).
OBJECTIVES: To evaluate outcomes and complication rates in CTEPH following pulmonary endarterectomy (PEA) for individuals receiving VKAs or DOACs.
METHODS: Consecutive CTEPH patients undergoing PEA between 2007 and 2018 were included in a retrospective analysis. Postoperative outcomes, recurrent venous thromboembolism (VTE), and bleeding events were obtained from patient medical records.
RESULTS: Seven hundred ninety-four individuals were treated with VKAs and 206 with DOACs following PEA. Mean observation period was 612 (standard deviation: 702) days. Significant improvements in hemodynamics and functional status were observed in both groups following PEA (P < .001). Major bleeding events were equivalent (P = 1) in those treated with VKAs (0.67%/person-year) and DOACs (0.68%/person-year). The VTE recurrence was proportionately higher (P = .008) with DOACs (4.62%/person-year) than VKAs (0.76%/person-year), although survival did not differ.
CONCLUSIONS: Post-PEA functional and hemodynamic outcomes appear unaffected by anticoagulant choice. Bleeding events were similar, but recurrent VTE rates significantly higher in those receiving DOACs. Our study provides a strong rationale for prospective registry data and/or studies to evaluate the safety of DOACs in CTEPH.

© 2019 International Society on Thrombosis and Haemostasis.
PMID 31557382
Hossein-Ardeschir Ghofrani, Gérald Simonneau, Andrea M D'Armini, Peter Fedullo, Luke S Howard, Xavier Jaïs, David P Jenkins, Zhi-Cheng Jing, Michael M Madani, Nicolas Martin, Eckhard Mayer, Kelly Papadakis, Dominik Richard, Nick H Kim, MERIT study investigators
Macitentan for the treatment of inoperable chronic thromboembolic pulmonary hypertension (MERIT-1): results from the multicentre, phase 2, randomised, double-blind, placebo-controlled study.
Lancet Respir Med. 2017 Oct;5(10):785-794. doi: 10.1016/S2213-2600(17)30305-3. Epub 2017 Sep 11.
Abstract/Text BACKGROUND: Macitentan is beneficial for long-term treatment of pulmonary arterial hypertension. The microvasculopathy of chronic thromboembolic pulmonary hypertension (CTEPH) and pulmonary arterial hypertension are similar.
METHODS: The phase 2, double-blind, randomised, placebo-controlled MERIT-1 trial assessed macitentan in 80 patients with CTEPH adjudicated as inoperable. Patients identified as WHO functional class II-IV with a pulmonary vascular resistance (PVR) of at least 400 dyn·s/cm5 and a walk distance of 150-450 m in 6 min were randomly assigned (1:1), via an interactive voice/web response system, to receive oral macitentan (10 mg once a day) or placebo. Treatment with phosphodiesterase type-5 inhibitors and oral or inhaled prostanoids was permitted for WHO functional class III/IV patients. The primary endpoint was resting PVR at week 16, expressed as percentage of PVR measured at baseline. Analyses were done in all patients who were randomly assigned to treatment; safety analyses were done in all patients who received at least one dose of the study drug. This study is registered with ClinicalTrials.gov, number NCT02021292.
FINDINGS: Between April 3, 2014, and March 17, 2016, we screened 186 patients for eligibility at 48 hospitals across 20 countries. Of these, 80 patients in 36 hospitals were randomly assigned to treatment (40 patients to macitentan, 40 patients to placebo). At week 16, geometric mean PVR decreased to 73·0% of baseline in the macitentan group and to 87·2% in the placebo group (geometric means ratio 0·84, 95% CI 0·70-0·99, p=0·041). The most common adverse events in the macitentan group were peripheral oedema (9 [23%] of 40 patients) and decreased haemoglobin (6 [15%]).
INTERPRETATION: In MERIT-1, macitentan significantly improved PVR in patients with inoperable CTEPH and was well tolerated.
FUNDING: Actelion Pharmaceuticals Ltd.

Copyright © 2017 Elsevier Ltd. All rights reserved.
PMID 28919201
Hossein-Ardeschir Ghofrani, Andrea M D'Armini, Friedrich Grimminger, Marius M Hoeper, Pavel Jansa, Nick H Kim, Eckhard Mayer, Gerald Simonneau, Martin R Wilkins, Arno Fritsch, Dieter Neuser, Gerrit Weimann, Chen Wang, CHEST-1 Study Group
Riociguat for the treatment of chronic thromboembolic pulmonary hypertension.
N Engl J Med. 2013 Jul 25;369(4):319-29. doi: 10.1056/NEJMoa1209657.
Abstract/Text BACKGROUND: Riociguat, a member of a new class of compounds (soluble guanylate cyclase stimulators), has been shown in previous clinical studies to be beneficial in the treatment of chronic thromboembolic pulmonary hypertension.
METHODS: In this phase 3, multicenter, randomized, double-blind, placebo-controlled study, we randomly assigned 261 patients with inoperable chronic thromboembolic pulmonary hypertension or persistent or recurrent pulmonary hypertension after pulmonary endarterectomy to receive placebo or riociguat. The primary end point was the change from baseline to the end of week 16 in the distance walked in 6 minutes. Secondary end points included changes from baseline in pulmonary vascular resistance, N-terminal pro-brain natriuretic peptide (NT-proBNP) level, World Health Organization (WHO) functional class, time to clinical worsening, Borg dyspnea score, quality-of-life variables, and safety.
RESULTS: By week 16, the 6-minute walk distance had increased by a mean of 39 m in the riociguat group, as compared with a mean decrease of 6 m in the placebo group (least-squares mean difference, 46 m; 95% confidence interval [CI], 25 to 67; P<0.001). Pulmonary vascular resistance decreased by 226 dyn·sec·cm(-5) in the riociguat group and increased by 23 dyn·sec·cm(-5) in the placebo group (least-squares mean difference, -246 dyn·sec·cm(-5); 95% CI, -303 to -190; P<0.001). Riociguat was also associated with significant improvements in the NT-proBNP level (P<0.001) and WHO functional class (P=0.003). The most common serious adverse events were right ventricular failure (in 3% of patients in each group) and syncope (in 2% of the riociguat group and in 3% of the placebo group).
CONCLUSIONS: Riociguat significantly improved exercise capacity and pulmonary vascular resistance in patients with chronic thromboembolic pulmonary hypertension. (Funded by Bayer HealthCare; CHEST-1 and CHEST-2 ClinicalTrials.gov numbers, NCT00855465 and NCT00910429, respectively.)

PMID 23883377
Nobuhiro Tanabe, Keiichi Fukuda, Hiromi Matsubara, Norifumi Nakanishi, Nobuhiro Tahara, Satoshi Ikeda, Takuya Kishi, Toru Satoh, Ken-Ichi Hirata, Teruo Inoue, Hiroshi Kimura, Yoshiaki Okano, Osamu Okazaki, Masataka Sata, Ichizo Tsujino, Shuichi Ueno, Norikazu Yamada, Atsushi Yao, Takayuki Kuriyama
Selexipag for Chronic Thromboembolic Pulmonary Hypertension in Japanese Patients - A Double-Blind, Randomized, Placebo-Controlled, Multicenter Phase II Study.
Circ J. 2020 Sep 25;84(10):1866-1874. doi: 10.1253/circj.CJ-20-0438. Epub 2020 Sep 3.
Abstract/Text BACKGROUND: Selexipag is an oral prostacyclin receptor (IP receptor) agonist with a non-prostanoid structure. This study examined its efficacy and safety in Japanese patients with non-operated or persistent/recurrent chronic thromboembolic pulmonary hypertension (CTEPH).Methods and Results:This Phase II study was a randomized, double-blind, placebo-controlled parallel-group comparison. The primary endpoint was a change in pulmonary vascular resistance (PVR) from baseline to week 17. The main analysis involved a per-protocol set group of 28 subjects. The change in PVR (mean±SD) after 17 weeks of treatment in the selexipag group was -104±191 dyn·s/cm5, whereas that in the placebo group was 26±180 dyn·s/cm5. Thus, the treatment effect after 17 weeks of selexipag treatment was calculated as -130±189 dyn·s/cm5(P=0.1553). Although the primary endpoint was not met, for the group not concomitantly using a pulmonary vasodilator the PVR in the selexipag group was significantly decreased compared with placebo group (P=0.0364). The selexipag group also showed improvement in total pulmonary resistance and cardiac index.
CONCLUSIONS: Selexipag treatment improved pulmonary hemodynamics in Japanese patients with CTEPH, but PVR did not show a significant difference between the selexipag and placebo groups. (Trial registration: JAPIC Clinical Trials Information [JapicCTI-111667]).

PMID 32879152
Takeshi Ogo, Hiroto Shimokawahara, Hideyuki Kinoshita, Seiichiro Sakao, Kohtaro Abe, Satoaki Matoba, Hirohiko Motoki, Noriaki Takama, Junya Ako, Yasuhiro Ikeda, Shuji Joho, Hisataka Maki, Takahiro Saeki, Teruyasu Sugano, Ichizo Tsujino, Koichiro Yoshioka, Naoki Shiota, Shinichi Tanaka, Chieko Yamamoto, Nobuhiro Tanabe, Koichiro Tatsumi, Study Group
Selexipag for the treatment of chronic thromboembolic pulmonary hypertension.
Eur Respir J. 2021 Nov 25;. doi: 10.1183/13993003.01694-2021. Epub 2021 Nov 25.
Abstract/Text Treatment options for inoperable chronic thromboembolic pulmonary hypertension (CTEPH) remain limited. Selexipag, an oral selective IP prostacyclin-receptor agonist approved for pulmonary arterial hypertension, is a potential treatment option for CTEPH.In this multicentre, randomised, double-blind, placebo-controlled study, 78 Japanese patients with inoperable CTEPH or persistent/recurrent pulmonary hypertension after pulmonary endarterectomy and/or balloon pulmonary angioplasty were randomly assigned to receive placebo or selexipag. The primary endpoint was the change in pulmonary vascular resistance (PVR) from baseline to week 20. The secondary endpoints were changes in other haemodynamic parameters, 6-min walk distance (6 WMD), Borg Dyspnoea Scale score, World Health Organisation (WHO) functional class, EuroQol 5 dimensions 5-level and N-terminal pro-brain natriuretic peptide.The change in PVR was -98.2±111.3 dyn·s·cm-5 and -4.6±163.6 dyn·s·cm-5 in the selexipag and placebo groups, respectively (mean difference, -93.5 dyn·s·cm-5; 95% confidence interval, -156.8, -30.3; p=0.006). The changes in cardiac index (p<0.001) and Borg Dyspnoea Scale score (p=0.036) were also significantly improved over placebo. 6WMD and WHO functional class were not significantly improved. The common adverse events in the selexipag group were corresponded to those generally observed following a prostacyclin analogue is administered.Selexipag significantly improved PVR and other haemodynamic variables in patients with CTEPH, although exercise capacity remained unchanged. Further large-scale investigation is necessary to prove the role of selexipag in CTEPH.

Copyright ©The authors 2021. For reproduction rights and permissions contact permissions@ersnet.org.
PMID 34824052
Takashi Kawakami, Aiko Ogawa, Katsumasa Miyaji, Hiroki Mizoguchi, Hiroto Shimokawahara, Takanori Naito, Takashi Oka, Kei Yunoki, Mitsuru Munemasa, Hiromi Matsubara
Novel Angiographic Classification of Each Vascular Lesion in Chronic Thromboembolic Pulmonary Hypertension Based on Selective Angiogram and Results of Balloon Pulmonary Angioplasty.
Circ Cardiovasc Interv. 2016 Oct;9(10). doi: 10.1161/CIRCINTERVENTIONS.115.003318.
Abstract/Text BACKGROUND: Balloon pulmonary angioplasty (BPA) is an alternative therapy for patients with chronic thromboembolic pulmonary hypertension who are ineligible for standard therapy, pulmonary endarterectomy. Although there are several classifications of vascular lesions, these classifications are based on the features of the specimen removed during pulmonary endarterectomy. Because organized thrombi are not removed during balloon pulmonary angioplasty, we attempted to establish a new classification of vascular lesions based on pulmonary angiographic images. We evaluated the success and complication rate of BPA in accordance with the location and morphology of thromboembolic lesions.
METHODS AND RESULTS: We reviewed 500 consecutive procedures (1936 lesions) of BPA in 97 patients with chronic thromboembolic pulmonary hypertension and investigated the outcomes of BPA based on the lesion distribution and the angiographic characteristics of the thromboembolic lesions, as follows: type A, ring-like stenosis lesion; type B, web lesion; type C, subtotal lesion; type D, total occlusion lesion, and type E, tortuous lesion. The success rate was higher, and the complication rate was lower in ring-like stenosis and web lesions. The total occlusion lesions had the lowest success rate. Tortuous lesions were associated with a high complication rate and should be treated only by operators with extensive experience with BPA.
CONCLUSIONS: We modified the previous angiographic classification and established a new classification for each vascular lesion. We clarified that the outcome and complication rate of the BPA are highly dependent on the lesion characteristics.

© 2016 American Heart Association, Inc.
PMID 27729418
J A Feinstein, S Z Goldhaber, J E Lock, S M Ferndandes, M J Landzberg
Balloon pulmonary angioplasty for treatment of chronic thromboembolic pulmonary hypertension.
Circulation. 2001 Jan 2;103(1):10-3.
Abstract/Text BACKGROUND: Although pulmonary thromboendarterectomy is increasingly successful for the definitive treatment of chronic thromboembolic pulmonary hypertension (CTEPH), not all patients have surgically accessible disease. Others are poor surgical candidates because of comorbid illness. Therefore, for selected patients, we defined and implemented an alternative interventional strategy of balloon pulmonary angioplasty (BPA).
METHODS AND RESULTS: Eighteen patients (mean age, 51.8 years; range, 14 to 75 years) with CTEPH underwent BPA; they averaged 2.6 procedures (range, 1 to 5) and 6 dilations (range, 1 to 12). Selection of pulmonary artery segments for dilation required (1) complete occlusion, (2) filling defects, or (3) signs of intravascular webs. After an average of 36 months of follow-up (range, 0.5 to 66 months), the average New York Heart Association class improved from 3.3 to 1.8 (P:<0.001), and 6-minute walking distances increased from 209 to 497 yards (P:<0.0001). Pulmonary artery mean pressures decreased from 43.0+/-12.1 to 33. 7+/-10.2 mm Hg (P:=0.007). Eleven patients developed reperfusion pulmonary edema; 3 required mechanical ventilation.
CONCLUSIONS: BPA reduces pulmonary artery hypertension in patients with CTEPH and is associated with long-term improvement in New York Heart Association class and 6-minute walking distances. BPA is a promising interventional technique that warrants randomized comparison with medical therapy in CTEPH patients who are not surgical candidates.

PMID 11136677
Hiroki Mizoguchi, Aiko Ogawa, Mitsuru Munemasa, Hiroshi Mikouchi, Hiroshi Ito, Hiromi Matsubara
Refined balloon pulmonary angioplasty for inoperable patients with chronic thromboembolic pulmonary hypertension.
Circ Cardiovasc Interv. 2012 Dec;5(6):748-55. doi: 10.1161/CIRCINTERVENTIONS.112.971077. Epub 2012 Nov 27.
Abstract/Text BACKGROUND: Although balloon pulmonary angioplasty (BPA) for inoperable patients with chronic thromboembolic pulmonary hypertension was first reported over a decade ago, its clinical application has been restricted because of limited efficacy and complications. We have refined the procedure of BPA to maximize its clinical efficacy.
METHODS AND RESULTS: Sixty-eight consecutive patients with inoperable chronic thromboembolic pulmonary hypertension underwent BPA. We evaluated pulmonary artery diameters and determined the appropriate balloon size by using intravascular ultrasound. We performed BPA in a staged fashion over multiple, separate procedures to maximize efficacy and reduce the risk of reperfusion pulmonary injury. A total of 4 (2-8) sessions were performed in each patient, and the number of vessels dilated per session was 3 (1-14). The World Health Organization functional class improved from 3 to 2 (P<0.01), and mean pulmonary arterial pressure was decreased from 45.4 ± 9.6 to 24.0 ± 6.4 mm Hg (P<0.01). One patient died because of right heart failure 28 days after BPA. During follow-up for 2.2 ± 1.4 years after the final BPA, another patient died of pneumonia, and the remaining 66 patients are alive. In 57 patients who underwent right heart catheterization at follow-up, improvement of mean pulmonary arterial pressure was maintained (24.0 ± 5.8 mm Hg at 1.0 ± 0.9 years). Forty-one patients (60%) developed reperfusion pulmonary injury after BPA, but mechanical ventilation was required in only 4 patients.
CONCLUSIONS: Our refined BPA procedure improves clinical status and hemodynamics of inoperable patients with chronic thromboembolic pulmonary hypertension, with a low mortality. A refined BPA procedure could be considered as a therapeutic approach for patients with inoperable chronic thromboembolic pulmonary hypertension.

PMID 23192917
Masaharu Kataoka, Takumi Inami, Kentaro Hayashida, Nobuhiko Shimura, Haruhisa Ishiguro, Takayuki Abe, Yuichi Tamura, Motomi Ando, Keiichi Fukuda, Hideaki Yoshino, Toru Satoh
Percutaneous transluminal pulmonary angioplasty for the treatment of chronic thromboembolic pulmonary hypertension.
Circ Cardiovasc Interv. 2012 Dec;5(6):756-62. doi: 10.1161/CIRCINTERVENTIONS.112.971390. Epub 2012 Nov 6.
Abstract/Text BACKGROUND: Chronic thromboembolic pulmonary hypertension leads to pulmonary hypertension and right-sided heart failure. The purpose of this study was to investigate the efficacy of percutaneous transluminal pulmonary angioplasty (PTPA) for the treatment of chronic thromboembolic pulmonary hypertension.
METHODS AND RESULTS: Twenty-nine patients with chronic thromboembolic pulmonary hypertension underwent PTPA. One patient had a wiring perforation as a complication of PTPA and died 2 days after the procedure. In the remaining 28 patients, PTPA did not produce immediate hemodynamic improvement at the time of the procedure. However, after follow-up (6.0 ± 6.9 months), New York Heart Association functional classifications and levels of plasma B-type natriuretic peptide significantly improved (both P<0.01). Hemodynamic parameters also significantly improved (mean pulmonary arterial pressure, 45.3 ± 9.8 versus 31.8 ± 10.0 mm Hg; cardiac output, 3.6 ± 1.2 versus 4.6 ± 1.7 L/min, baseline versus follow-up, respectively; both P<0.01). Twenty-seven of 51 procedures in total (53%), and 19 of 28 first procedures (68%), had reperfusion pulmonary edema as the chief complication. Patients with severe clinical signs and/or severe hemodynamics at baseline had a high risk of reperfusion pulmonary edema.
CONCLUSIONS: PTPA improved subjective symptoms and objective variables, including pulmonary hemodynamics. PTPA may be a promising therapeutic strategy for the treatment of chronic thromboembolic pulmonary hypertension.
CLINICAL TRIAL REGISTRATION: URL: http://www.umin.ac.jp. Unique identifier: UMIN000001572.

PMID 23132237

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