Monographic Issue on Pulmonary Hypertension: Medical and Interventional Treatment for Chronic Thromboembolic Pulmonary Hypertension

Marion Delcroix; Catharina Belge; Geert Maleux; Laurent Godinas

doi:10.1055/s-0043-1770122

Seminars in Respiratory and Critical Care Medicine, Inhaltsverzeichnis

Semin Respir Crit Care Med 2023; 44(06): 840-850
DOI: 10.1055/s-0043-1770122

Review Article

Monographic Issue on Pulmonary Hypertension: Medical and Interventional Treatment for Chronic Thromboembolic Pulmonary Hypertension

Marion Delcroix

¹Clinical Department of Respiratory Diseases, Department of Chronic Diseases and Metabolism (CHROMETA), Laboratory of Respiratory Diseases and Thoracic Surgery (BREATHE), KU Leuven-University of Leuven, University Hospitals of Leuven, Leuven, Belgium

²European Reference Network on Rare Pulmonary Diseases (ERN-LUNG), Belgium

,

Catharina Belge

¹Clinical Department of Respiratory Diseases, Department of Chronic Diseases and Metabolism (CHROMETA), Laboratory of Respiratory Diseases and Thoracic Surgery (BREATHE), KU Leuven-University of Leuven, University Hospitals of Leuven, Leuven, Belgium

²European Reference Network on Rare Pulmonary Diseases (ERN-LUNG), Belgium

,

Geert Maleux

³Clinical Department of Radiology, University Hospitals of Leuven, Leuven, Belgium

,

Laurent Godinas

¹Clinical Department of Respiratory Diseases, Department of Chronic Diseases and Metabolism (CHROMETA), Laboratory of Respiratory Diseases and Thoracic Surgery (BREATHE), KU Leuven-University of Leuven, University Hospitals of Leuven, Leuven, Belgium

²European Reference Network on Rare Pulmonary Diseases (ERN-LUNG), Belgium

› Institutsangaben

Abstract

Chronic thromboembolic pulmonary hypertension (CTEPH) is a rare complication of acute pulmonary embolism. The reasons why clots do not resorb are incompletely understood, but the result is partial or complete fibrothrombotic obstruction of pulmonary arteries. A secondary microvasculopathy aggravates the pulmonary hypertension (PH) as a consequence of high flow and shear stress in the nonoccluded arteries. The treatment of CTEPH has long been purely surgical, but many patients were inoperable because of inaccessible lesions or severe comorbidities. Alternatives were developed, including medical therapy and more recently balloon pulmonary angioplasty (BPA). Depending on the generation of the obstructed vessels, the treatment will be surgical, up to the (sub)segmental level, or by BPA for more distal vessels. PH drugs are used to treat the microvasculopathy. The current paper describes the therapeutic management of inoperable patients: the medical approach with PH drugs used in mono- or combination therapy; the proper use of anticoagulants in CTEPH; the technique, indications, and results at short- and long-term of BPA; the multimodal approach for inoperable patients combining PH drugs and BPA; and the effects of rehabilitation. It shows the importance of a multidisciplinary approach to the disease.

Keywords

CTEPH - balloon pulmonary angioplasty - medical treatment - anticoagulation

Volltext

Referenzen

References
1 Ende-Verhaar YM, Cannegieter SC, Vonk Noordegraaf A. et al. Incidence of chronic thromboembolic pulmonary hypertension after acute pulmonary embolism: a contemporary view of the published literature. Eur Respir J 2017; 49 (02) 1601792
2 Valerio L, Mavromanoli AC, Barco S. et al; FOCUS Investigators. Chronic thromboembolic pulmonary hypertension and impairment after pulmonary embolism: the FOCUS study. Eur Heart J 2022; 43 (36) 3387-3398
3 Coquoz N, Weilenmann D, Stolz D. et al. Multicentre observational screening survey for the detection of CTEPH following pulmonary embolism. Eur Respir J 2018; 51 (04) 1702505
4 Simonneau G, Torbicki A, Dorfmüller P, Kim N. The pathophysiology of chronic thromboembolic pulmonary hypertension. Eur Respir Rev 2017; 26 (143) 160112
5 Azarian R, Wartski M, Collignon MA. et al. Lung perfusion scans and hemodynamics in acute and chronic pulmonary embolism. J Nucl Med 1997; 38 (06) 980-983
6 Humbert M, Kovacs G, Hoeper MM. et al; ESC/ERS Scientific Document Group. 2022 ESC/ERS guidelines for the diagnosis and treatment of pulmonary hypertension. Eur Respir J 2023; 61 (01) 2200879
7 Humbert M, Kovacs G, Hoeper MM. et al; ESC/ERS Scientific Document Group. 2022 ESC/ERS guidelines for the diagnosis and treatment of pulmonary hypertension. Eur Heart J 2022; 43 (38) 3618-3731
8 Pepke-Zaba J, Delcroix M, Lang I. et al. Chronic thromboembolic pulmonary hypertension (CTEPH): results from an international prospective registry. Circulation 2011; 124 (18) 1973-1981
9 Lang IM, Simonneau G, Pepke-Zaba JW. et al. Factors associated with diagnosis and operability of chronic thromboembolic pulmonary hypertension. A case-control study. Thromb Haemost 2013; 110 (01) 83-91
10 Bonderman D, Wilkens H, Wakounig S. et al. Risk factors for chronic thromboembolic pulmonary hypertension. Eur Respir J 2009; 33 (02) 325-331
11 Delcroix M, Torbicki A, Gopalan D. et al. ERS statement on chronic thromboembolic pulmonary hypertension. Eur Respir J 2021; 57 (06) 2002828
12 Helmersen D, Provencher S, Hirsch AM. et al. Diagnosis of chronic thromboembolic pulmonary hypertension: a Canadian Thoracic Society clinical practice guideline update. Can J Respir Critical Care Sleep Medicine [Internet] 2019; 3 (04) 177-198
13 Remy-Jardin M, Ryerson CJ, Schiebler ML. et al. Imaging of pulmonary hypertension in adults: a position paper from the Fleischner society. Radiology 2021; 298 (03) 531-549
14 Kawakami T, Ogawa A, Miyaji K. et al. 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; 9 (10) e003318
15 Auger WR, Fedullo PF, Moser KM, Buchbinder M, Peterson KL. Chronic major-vessel thromboembolic pulmonary artery obstruction: appearance at angiography. Radiology 1992; 182 (02) 393-398
16 Skoro-Sajer N, Hack N, Sadushi-Koliçi R. et al. Pulmonary vascular reactivity and prognosis in patients with chronic thromboembolic pulmonary hypertension: a pilot study. Circulation 2009; 119 (02) 298-305
17 Ghofrani H-A, D'Armini AM, Grimminger F. et al; CHEST-1 Study Group. Riociguat for the treatment of chronic thromboembolic pulmonary hypertension. N Engl J Med 2013; 369 (04) 319-329
18 Simonneau G, D'Armini AM, Ghofrani HA. et al. Riociguat for the treatment of chronic thromboembolic pulmonary hypertension: a long-term extension study (CHEST-2). Eur Respir J 2015; 45 (05) 1293-1302
19 Sadushi-Koliçi R, Jansa P, Kopeć G. et al. Subcutaneous treprostinil for the treatment of severe non-operable chronic thromboembolic pulmonary hypertension (CTREPH): a double-blind, phase 3, randomised controlled trial. Lancet Respir Med 2019; 7 (03) 239-248
20 Suntharalingam J, Treacy CM, Doughty NJ. et al. Long-term use of sildenafil in inoperable chronic thromboembolic pulmonary hypertension. Chest 2008; 134 (02) 229-236
21 Jaïs X, D'Armini AM, Jansa P. et al; Bosentan Effects in iNopErable Forms of chronIc Thromboembolic pulmonary hypertension Study Group. Bosentan for treatment of inoperable chronic thromboembolic pulmonary hypertension: BENEFiT (Bosentan Effects in iNopErable Forms of chronIc Thromboembolic pulmonary hypertension), a randomized, placebo-controlled trial. J Am Coll Cardiol 2008; 52 (25) 2127-2134
22 Delcroix M, Lang I, Pepke-Zaba J. et al. Long-term outcome of patients with chronic thromboembolic pulmonary hypertension: results from an international prospective registry. Circulation 2016; 133 (09) 859-871
23 Delcroix M, Staehler G, Gall H. et al. Risk assessment in medically treated chronic thromboembolic pulmonary hypertension patients. Eur Respir J 2018; 52 (05) 1800248
24 Guth S, D'Armini AM, Delcroix M. et al. Current strategies for managing chronic thromboembolic pulmonary hypertension: results of the worldwide prospective CTEPH registry. ERJ Open Res 2021; 7 (03) 00850-02020
25 Kerr KM, Elliott CG, Chin K. et al. Results from the United States chronic thromboembolic pulmonary hypertension registry: enrollment characteristics and 1-year follow-up. Chest 2021; 160 (05) 1822-1831
26 Ghofrani H-A, Simonneau G, D'Armini AM. et al; 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; 5 (10) 785-794
27 Galiè N, Barberà JA, Frost AE. et al; AMBITION Investigators. Initial use of ambrisentan plus tadalafil in pulmonary arterial hypertension. N Engl J Med 2015; 373 (09) 834-844
28 Gabrielly M, Bourlier D, Taniguchi Y. et al. Initial dual oral combination therapy in inoperable chronic thromboembolic pulmonary hypertension (CTEPH). Eur Respir J 2018; 52 (suppl 62): PA3053
29 van Thor MCJ, Snijder RJ, Kelder JC, Mager JJ, Post MC. Does combination therapy work in chronic thromboembolic pulmonary hypertension?. Int J Cardiol Heart Vasc 2020; 29: 100544
30 Pepke-Zaba J, Jansa P, Kim NH, Naeije R, Simonneau G. Chronic thromboembolic pulmonary hypertension: role of medical therapy. Eur Respir J 2013; 41 (04) 985-990
31 Bunclark K, Newnham M, Chiu YD. et al. A multicenter study of anticoagulation in operable chronic thromboembolic pulmonary hypertension. J Thromb Haemost 2020; 18 (01) 114-122
32 Sedhom R, Megaly M, Gupta E, Amanullah A. Use of direct oral anticoagulants in chronic thromboembolic pulmonary hypertension: a systematic review. J Thromb Thrombolysis 2022; 53 (01) 51-57
33 Sena S, Bulent M, Derya K. et al. 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; 10 (01) 20 45894019873545
34 Humbert M, Simonneau G, Pittrow D. et al. Oral anticoagulants (NOAC and VKA) in chronic thromboembolic pulmonary hypertension. J Heart Lung Transplant 2022; 41 (06) 716-721
35 Jeong I, Alotaibi M, Fernandes TM. et al. Direct oral anticoagulants in patients with chronic thromboembolic pulmonary hypertension and the presence of recent thrombus during pulmonary endarterectomy. Pulm Circ 2022; 12 (03) e12110
36 Frey R, Becker C, Saleh S, Unger S, van der Mey D, Mück W. Clinical pharmacokinetic and pharmacodynamic profile of riociguat. Clin Pharmacokinet 2018; 57 (06) 647-661
37 Dingemanse J, van Giersbergen PLM. Clinical pharmacology of bosentan, a dual endothelin receptor antagonist. Clin Pharmacokinet 2004; 43 (15) 1089-1115
38 Bertoletti L, Mismetti V, Giannakoulas G. Use of anticoagulants in patients with pulmonary hypertension. Hamostaseologie 2020; 40 (03) 348-355
39 Konstantinides SV, Meyer G, Becattini C. et al; 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 (04) 543-603
40 Pengo V, Denas G, Zoppellaro G. et al. Rivaroxaban vs warfarin in high-risk patients with antiphospholipid syndrome. Blood 2018; 132 (13) 1365-1371
41 Khairani CD, Bejjani A, Piazza G. et al. Direct oral anticoagulants vs vitamin K antagonists in patients with antiphospholipid syndromes: meta-analysis of randomized trials. J Am Coll Cardiol 2023; 81 (01) 16-30
42 Rosenkranz S, Howard LS, Gomberg-Maitland M, Hoeper MM. Systemic consequences of pulmonary hypertension and right-sided heart failure. Circulation 2020; 141 (08) 678-693
43 Mahmud E, Patel M, Ang L, Poch D. Advances in balloon pulmonary angioplasty for chronic thromboembolic pulmonary hypertension. Pulm Circ 2021; 11 (02) 20 458940211007385
44 Minatsuki S, Kiyosue A, Kodera S. et al. Novel balloon pulmonary angioplasty technique for chronic thromboembolic pulmonary hypertension. Int Heart J 2020; 61 (05) 999-1004
45 Inohara T, Kawakami T, Kataoka M. et al. Lesion morphological classification by OCT to predict therapeutic efficacy after balloon pulmonary angioplasty in CTEPH. Int J Cardiol 2015; 197: 23-25
46 Inami T, Kataoka M, Shimura N. et al. Pulmonary edema predictive scoring index (PEPSI), a new index to predict risk of reperfusion pulmonary edema and improvement of hemodynamics in percutaneous transluminal pulmonary angioplasty. JACC Cardiovasc Interv 2013; 6 (07) 725-736
47 Mizoguchi H, Ogawa A, Munemasa M, Mikouchi H, Ito H, Matsubara H. Refined balloon pulmonary angioplasty for inoperable patients with chronic thromboembolic pulmonary hypertension. Circ Cardiovasc Interv 2012; 5 (06) 748-755
48 Tabuchi I, Ogawa A, Shigetoshi M, Shimokawahara H, Ito H, Matsubara H. Low incidence of restenosis after successful balloon pulmonary angioplasty in patients with chronic thromboembolic pulmonary hypertension. Cardiovasc Intervention Ther 2023; 38 (02) 231-240
49 Tatebe S, Fukumoto Y, Sugimura K. et al. Optical coherence tomography as a novel diagnostic tool for distal type chronic thromboembolic pulmonary hypertension. Circ J 2010; 74 (08) 1742-1744
50 Brenot P, Jaïs X, Taniguchi Y. et al. French experience of balloon pulmonary angioplasty for chronic thromboembolic pulmonary hypertension. Eur Respir J 2019; 53 (05) 1802095
51 Cannon JE, Su L, Kiely DG. et al. Dynamic risk stratification of patient long-term outcome after pulmonary endarterectomy: results from the United Kingdom national cohort. Circulation 2016; 133 (18) 1761-1771
52 Shimokawahara H, Nagayoshi S, Ogawa A, Matsubara H. Continual improvement in pressure gradient at the lesion after balloon pulmonary angioplasty for chronic thromboembolic pulmonary hypertension. Can J Cardiol 2021; 37 (08) 1232-1239
53 Galiè N, Humbert M, Vachiery J-L. et al. 2015 ESC/ERS guidelines for the diagnosis and treatment of pulmonary hypertension. Eur Respir J 2015; 46 (04) 903-975
54 Galiè N, Humbert M, Vachiery J-L. et al; ESC Scientific Document Group. 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; 37 (01) 67-119
55 Darocha S, Araszkiewicz A, Kurzyna M. et al. Balloon pulmonary angioplasty in technically operable and technically inoperable chronic thromboembolic pulmonary hypertension. J Clin Med 2021; 10 (05) 1038
56 Darocha S, Pietura R, Banaszkiewicz M. et al. Balloon pulmonary angioplasty with stent implantation as a treatment of proximal chronic thromboembolic pulmonary hypertension. Diagnostics (Basel) 2020; 10 (06) 363
57 Shimura N, Kataoka M, Inami T. et al. Additional percutaneous transluminal pulmonary angioplasty for residual or recurrent pulmonary hypertension after pulmonary endarterectomy. Int J Cardiol 2015; 183: 138-142
58 Araszkiewicz A, Darocha S, Pietrasik A. et al. Balloon pulmonary angioplasty for the treatment of residual or recurrent pulmonary hypertension after pulmonary endarterectomy. Int J Cardiol 2019; 278: 232-237
59 Ito R, Yamashita J, Sasaki Y. et al. Efficacy and safety of balloon pulmonary angioplasty for residual pulmonary hypertension after pulmonary endarterectomy. Int J Cardiol 2021; 334: 105-109
60 Hug KP, Gerry Coghlan J, Cannon J. et al. Serial right heart catheter assessment between balloon pulmonary angioplasty sessions identify procedural factors that influence response to treatment. J Heart Lung Transplant 2021; 40 (10) 1223-1234
61 Godinas L, Verbelen T, Delcroix M. Residual pulmonary hypertension after pulmonary thromboendarterectomy: incidence, pathogenesis and therapeutic options. Ann Cardiothorac Surg 2021
62 Shimokawahara H, Ogawa A, Matsubara H. Balloon pulmonary angioplasty for chronic thromboembolic pulmonary hypertension: advances in patient and lesion selection. Curr Opin Pulm Med 2021; 27 (05) 303-310
63 Amsallem M, Guihaire J, Arthur Ataam J. et al. Impact of the initiation of balloon pulmonary angioplasty program on referral of patients with chronic thromboembolic pulmonary hypertension to surgery. J Heart Lung Transplant 2018; 37 (09) 1102-1110
64 Madani MM. Pulmonary endarterectomy for chronic thromboembolic pulmonary hypertension: state-of-the-art 2020. Pulm Circ 2021; 11 (02) 20 458940211007372
65 Wiedenroth CB, Olsson KM, Guth S. et al. Balloon pulmonary angioplasty for inoperable patients with chronic thromboembolic disease. Pulm Circ 2018; 8 (01) 20 45893217753122
66 Inami T, Kataoka M, Kikuchi H, Goda A, Satoh T. Balloon pulmonary angioplasty for symptomatic chronic thromboembolic disease without pulmonary hypertension at rest. Int J Cardiol 2019; 289: 116-118
67 Voorburg JA, Cats VM, Buis B, Bruschke AV. Balloon angioplasty in the treatment of pulmonary hypertension caused by pulmonary embolism. Chest 1988; 94 (06) 1249-1253
68 Feinstein JA, Goldhaber SZ, Lock JE, Ferndandes SM, Landzberg MJ. Balloon pulmonary angioplasty for treatment of chronic thromboembolic pulmonary hypertension. Circulation 2001; 103 (01) 10-13
69 Kataoka M, Inami T, Hayashida K. et al. Percutaneous transluminal pulmonary angioplasty for the treatment of chronic thromboembolic pulmonary hypertension. Circ Cardiovasc Interv 2012; 5 (06) 756-762
70 Hoole SP, Coghlan JG, Cannon JE. et al. Balloon pulmonary angioplasty for inoperable chronic thromboembolic pulmonary hypertension: the UK experience. Open Heart 2020; 7 (01) e001144
71 Godinas L, Bonne L, Budts W. et al. Balloon pulmonary angioplasty for the treatment of nonoperable chronic thromboembolic pulmonary hypertension: single-center experience with low initial complication rate. J Vasc Interv Radiol 2019; 30 (08) 1265-1272
72 Ogawa A, Satoh T, Fukuda T. et al. Balloon pulmonary angioplasty for chronic thromboembolic pulmonary hypertension: results of a multicenter registry. Circ Cardiovasc Qual Outcomes 2017; 10 (11) e004029
73 Fukui S, Ogo T, Morita Y. et al. Right ventricular reverse remodelling after balloon pulmonary angioplasty. Eur Respir J 2014; 43 (05) 1394-1402
74 Broch K, Murbraech K, Ragnarsson A. et al. Echocardiographic evidence of right ventricular functional improvement after balloon pulmonary angioplasty in chronic thromboembolic pulmonary hypertension. J Heart Lung Transplant 2016; 35 (01) 80-86
75 Tsugu T, Murata M, Kawakami T. et al. Significance of echocardiographic assessment for right ventricular function after balloon pulmonary angioplasty in patients with chronic thromboembolic induced pulmonary hypertension. Am J Cardiol 2015; 115 (02) 256-261
76 Sato H, Ota H, Sugimura K. et al. Balloon pulmonary angioplasty improves biventricular functions and pulmonary flow in chronic thromboembolic pulmonary hypertension. Circ J 2016; 80 (06) 1470-1477
77 Yamasaki Y, Nagao M, Abe K. et al. Balloon pulmonary angioplasty improves interventricular dyssynchrony in patients with inoperable chronic thromboembolic pulmonary hypertension: a cardiac MR imaging study. Int J Cardiovasc Imaging 2017; 33 (02) 229-239
78 Schoenfeld C, Hinrichs JB, Olsson KM. et al. Cardio-pulmonary MRI for detection of treatment response after a single BPA treatment session in CTEPH patients. Eur Radiol 2019; 29 (04) 1693-1702
79 Marchetta S, Verbelen T, Claessen G, Quarck R, Delcroix M, Godinas L. A comprehensive assessment of right ventricular function in chronic thromboembolic pulmonary hypertension. J Clin Med 2022; 12 (01) 47
80 Fujii S, Nagayoshi S, Ogawa K. et al. A pilot cohort study assessing the feasibility of complete revascularization with balloon pulmonary angioplasty for chronic thromboembolic pulmonary hypertension. PLoS One 2021; 16 (07) e0254770
81 Blanquez-Nadal M, Piliero N, Guillien A. et al. Exercise hyperventilation and pulmonary gas exchange in chronic thromboembolic pulmonary hypertension: effects of balloon pulmonary angioplasty. J Heart Lung Transplant 2022; 41 (01) 70-79
82 Miura K, Katsumata Y, Kawakami T. et al. Exercise tolerance and quality of life in hemodynamically partially improved patients with chronic thromboembolic pulmonary hypertension treated with balloon pulmonary angioplasty. PLoS One 2021; 16 (07) e0255180
83 Aoki T, Sugimura K, Tatebe S. et al. Comprehensive evaluation of the effectiveness and safety of balloon pulmonary angioplasty for inoperable chronic thrombo-embolic pulmonary hypertension: long-term effects and procedure-related complications. Eur Heart J 2017; 38 (42) 3152-3159
84 Minatsuki S, Kodera S, Kiyosue A. et al. Balloon pulmonary angioplasty improves quality of life in Japanese patients with chronic thromboembolic pulmonary hypertension. J Cardiol 2020; 76 (02) 205-210
85 Darocha S, Pietura R, Pietrasik A. et al. Improvement in quality of life and hemodynamics in chronic thromboembolic pulmonary hypertension treated with balloon pulmonary angioplasty. Circ J 2017; 81 (04) 552-557
86 Taniguchi Y, Jaïs X, Jevnikar M. et al. Predictors of survival in patients with not-operated chronic thromboembolic pulmonary hypertension. J Heart Lung Transplant 2019; 38 (08) 833-842
87 Wiedenroth CB, Rolf A, Steinhaus K. et al. Riociguat and balloon pulmonary angioplasty improve prognosis in patients with inoperable chronic thromboembolic pulmonary hypertension. J Heart Lung Transplant 2023; 42 (01) 134-139
88 Ejiri K, Ogawa A, Fujii S, Ito H, Matsubara H. Vascular injury is a major cause of lung injury after balloon pulmonary angioplasty in patients with chronic thromboembolic pulmonary hypertension. Circ Cardiovasc Interv 2018; 11 (12) e005884
89 Ejiri K, Ogawa A, Matsubara H. Bail-out technique for pulmonary artery rupture with a covered stent in balloon pulmonary angioplasty for chronic thromboembolic pulmonary hypertension. JACC Cardiovasc Interv 2015; 8 (05) 752-753
90 Lang I, Meyer BC, Ogo T. et al. Balloon pulmonary angioplasty in chronic thromboembolic pulmonary hypertension. Eur Respir Rev 2017; 26 (143) 160119
91 Jaïs X, Brenot P, Bouvaist H. et al. Balloon pulmonary angioplasty versus riociguat for the treatment of inoperable chronic thromboembolic pulmonary hypertension (RACE): a multicentre, phase 3, open-label, randomised controlled trial and ancillary follow-up study. Lancet Respir Med 2022; 10 (10) 961-971
92 Grünig E, Eichstaedt C, Barberà J-A. et al. ERS statement on exercise training and rehabilitation in patients with severe chronic pulmonary hypertension. Eur Respir J 2019; 53 (02) 1800332
93 Nagel C, Prange F, Guth S. et al. Exercise training improves exercise capacity and quality of life in patients with inoperable or residual chronic thromboembolic pulmonary hypertension. PLoS One 2012; 7 (07) e41603
94 Inagaki T, Terada J, Tanabe N. et al. Home-based pulmonary rehabilitation in patients with inoperable or residual chronic thromboembolic pulmonary hypertension: a preliminary study. Respir Investig 2014; 52 (06) 357-364
95 Fukui S, Ogo T, Takaki H. et al. Efficacy of cardiac rehabilitation after balloon pulmonary angioplasty for chronic thromboembolic pulmonary hypertension. Heart 2016; 102 (17) 1403-1409
96 Olsson KM, Wiedenroth CB, Kamp JC. et al. Balloon pulmonary angioplasty for inoperable patients with chronic thromboembolic pulmonary hypertension: the initial German experience. Eur Respir J 2017; 49 (06) 1602409
97 Poch DS, Mahmud E, Patel M. et al. Patient selection for balloon pulmonary angioplasty: six-year results from a high volume PTE surgical center. Pulm Circ 2022; 12 (04) e12148