Aktuelle Definition und Diagnostik der pulmonalen Hypertonie

T. J. Lange; M. Borst; R. Ewert; M. Halank; H. Klose; H. Leuchte; F. J. Meyer; H.-J. Seyfarth; D. Skowasch; H. Wilkens; M. Held

doi:10.1055/a-1199-1548

Pneumologie, Inhaltsverzeichnis

Pneumologie 2020; 74(12): 847-863
DOI: 10.1055/a-1199-1548

Übersicht

Aktuelle Definition und Diagnostik der pulmonalen Hypertonie

Current Aspects of Definition and Diagnosis of Pulmonary Hypertension

T. J. Lange

¹Uniklinik Regensburg, Klinik für Innere Medizin II, Bereich Pneumologie, Regensburg

,

M. Borst

²Medizinische Klinik I, Caritas-Krankenhaus, Bad Mergentheim

,

R. Ewert

³Pneumologie, Uniklinik Greifswald, Greifwald

,

M. Halank

⁴Universitätsklinikum Carl Gustav Carus, Medizinische Klinik 1, Bereich Pneumologie, Dresden

,

H. Klose

⁵Universitätsklinikum Hamburg-Eppendorf, Abteilung für Pneumologie, Hamburg

,

H. Leuchte

⁶Klinik der Barmherzigen Schwestern, Krankenhaus Neuwittelsbach, Lehrkrankenhaus der LMU München, München

,

F. J. Meyer

⁷Lungenzentrum München (Bogenhausen-Harlaching), München Klinik gGmbH, München

,

H.-J. Seyfarth

⁸Bereich Pneumologie, Universitätsklinikum Leipzig, Leipzig

,

D. Skowasch

⁹Universitätsklinikum Bonn, Medizinische Klinik II, Sektion Pneumologie, Bonn

,

H. Wilkens

¹⁰Klinik für Innere Medizin V, Universitätsklinikum des Saarlandes, Homburg

,

M. Held

¹¹Medizinische Klinik mit Schwerpunkt Pneumologie und Beatmungsmedizin, Klinikum Würzburg Mitte, Standort Missioklinik, Würzburg

› Institutsangaben

Abstract

Zusammenfassung

Die 6. Weltkonferenz für pulmonale Hypertonie (PH) fand vom 27. 2. – 1. 3. 2018 in Nizza statt. Hier wurden die Erkenntnisse auf dem Gebiet der PH der letzten 5 Jahre nach Aufarbeitung und Diskussion über einen längeren Vorbereitungszeitraum von 13 Arbeitsgruppen präsentiert und in der Folge zum Jahreswechsel 2018/2019 publiziert. Einer der seither intensiv diskutierten Vorschläge ist der einer Änderung der hämodynamischen Definition der PH mit Absenkung des Grenzwertes für den mittleren pulmonalarteriellen Druck von ≥ 25 auf > 20 mmHg, gemessen im Rechtsherzkatheter in Ruhe. Zusätzlich wurde der pulmonalvaskuläre Widerstand in die PH-Definition aufgenommen, was die Wichtigkeit der Bestimmung des Herzzeitvolumens während der Rechtsherzkatheteruntersuchung unterstreicht.

Die Rationale sowie mögliche Auswirkungen der neuen PH-Definition, zu welchen zwischenzeitlich bereits neue Publikationen erschienen sind, möchten wir in diesem Übersichtsartikel diskutieren. Ferner ist ein aktueller Überblick zur nicht-invasiven und invasiven Diagnostik der PH enthalten, in welchem auf den Stellenwert der Methoden für Diagnostik, Differenzialdiagnostik und Prognose sowie weitere Neuerungen der 6. PH-Weltkonferenz eingegangen wird. Ergänzt haben wir einen Abschnitt zum Stellenwert von Belastungsuntersuchungen für das Erkennen und die Verlaufsbeurteilung der PH, welche bei der Diskussion in Nizza und in den nachfolgenden Publikationen zumindest erwähnt, aber nicht ausführlicher besprochen wurden.

Abstract

At the 6th World Symposium on Pulmonary Hypertension (WSPH), which took place from February 27 until March 1, 2018 in Nice, scientific progress over the past 5 years in the field of pulmonary hypertension (PH) was presented by 13 working groups. The results of the discussion were published as proceedings towards the end of 2018. One of the major changes suggested by the WSPH was the lowering of the diagnostic threshold for PH from ≥ 25 to > 20 mmHg mean pulmonary arterial pressure, measured by right heart catheterization at rest. In addition, the pulmonary vascular resistance was introduced into the definition of PH, which underlines the importance of cardiac output determination at the diagnostic right heart catheterization.

In this article, we discuss the rationale and possible consequences of a changed PH definition in the context of the current literature. Further, we provide a current overview on non-invasive and invasive methods for diagnosis, differential diagnosis, and prognosis of PH, including exercise tests.

Volltext

Referenzen

Literatur
1 Galiè N, Humbert M, Vachiery J-L. et al. 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 Respir J 2015; 46: 903-975
2 Simonneau G, Montani D, Celermajer DS. et al. Haemodynamic definitions and updated clinical classification of pulmonary hypertension. Eur Respir J 2019; 53
3 Badesch DB, Champion HC, Gomez Sanchez MA. et al. Diagnosis and Assessment of Pulmonary Arterial Hypertension. J Am Coll Cardiol 2009; 54 (Suppl. 01) S55-S66
4 Douschan P, Kovacs G, Avian A. et al. Mild Elevation of Pulmonary Arterial Pressure as a Predictor of Mortality. Am J Respir Crit Care Med 2018; 197: 509-516
5 Maron BA, Hess E, Maddox TM. et al. Association of Borderline Pulmonary Hypertension With Mortality and Hospitalization in a Large Patient Cohort: Insights From the Veterans Affairs Clinical Assessment, Reporting, and Tracking Program. Circulation 2016; 133: 1240-1248
6 Kolte D, Lakshmanan S, Jankowich MD. et al. Mild Pulmonary Hypertension Is Associated With Increased Mortality: A Systematic Review and Meta-Analysis. J Am Heart Assoc 2018; 7: e009729
7 Coghlan JG, Denton CP, Grünig E. et al. Evidence-based detection of pulmonary arterial hypertension in systemic sclerosis: the DETECT study. Ann Rheum Dis 2014; 73: 1340-1349
8 Hoffmann-Vold A-M, Fretheim H, Midtvedt Ø. et al. Frequencies of borderline pulmonary hypertension before and after the DETECT algorithm: results from a prospective systemic sclerosis cohort. Rheumatol Oxf Engl 2018; 57: 480-487
9 Dumitrescu D, Nagel C, Kovacs G. et al. Cardiopulmonary exercise testing for detecting pulmonary arterial hypertension in systemic sclerosis. Heart Br Card Soc 2017; 103 (10) 774-782
10 Lau EMT, Vanderpool RR, Choudhary P. et al. Dobutamine stress echocardiography for the assessment of pressure-flow relationships of the pulmonary circulation. Chest 2014; 146: 959-966
11 Grünig E, Weissmann S, Ehlken N. et al. Stress Doppler echocardiography in relatives of patients with idiopathic and familial pulmonary arterial hypertension: results of a multicenter European analysis of pulmonary artery pressure response to exercise and hypoxia. Circulation 2009; 119: 1747-1757
12 Argiento P, Chesler N, Mulè M. et al. Exercise stress echocardiography for the study of the pulmonary circulation. Eur Respir J 2010; 35: 1273-1278
13 Argiento P, Vanderpool RR, Mulè M. et al. Exercise stress echocardiography of the pulmonary circulation: limits of normal and sex differences. Chest 2012; 142: 1158-1165
14 Hoeper MM, Bogaard HJ, Condliffe R. et al. Definitions and diagnosis of pulmonary hypertension. J Am Coll Cardiol 2013; 62: D42-50
15 Crawford TC, Leary PJ, Fraser CD. et al. Impact of the New Pulmonary Hypertension Definition on Heart Transplant Outcomes: Expanding the Hemodynamic Risk Profile. Chest 2019;
16 Caravita S, Dewachter C, Soranna D. et al. Haemodynamics to predict outcome in pulmonary hypertension due to left heart disease: a meta-analysis. Eur Respir J 2018; 51
17 Xanthouli P, Jordan S, Milde N. et al. Haemodynamic phenotypes and survival in patients with systemic sclerosis: the impact of the new definition of pulmonary arterial hypertension. Ann Rheum Dis 2019;
18 Kovacs G, Berghold A, Scheidl S. et al. Pulmonary arterial pressure during rest and exercise in healthy subjects: a systematic review. Eur Respir J 2009; 34: 888-894
19 Kim NH, Delcroix M, Jais X. et al. Chronic thromboembolic pulmonary hypertension. Eur Respir J 2019; 53
20 Taboada D, Pepke-Zaba J, Jenkins DP. et al. Outcome of pulmonary endarterectomy in symptomatic chronic thromboembolic disease. Eur Respir J 2014; 44: 1635-1645
21 Ghofrani H-A, D’Armini AM, Grimminger F. et al. Riociguat for the treatment of chronic thromboembolic pulmonary hypertension. N Engl J Med 2013; 369: 319-329
22 Jaafar S, Visovatti S, Young A. et al. Impact of the revised haemodynamic definition on the diagnosis of pulmonary hypertension in patients with systemic sclerosis. Eur Respir J 2019; 54
23 Barst RJ, McGoon M, Torbicki A. et al. Diagnosis and differential assessment of pulmonary arterial hypertension. J Am Coll Cardiol 2004; 43: 40S-47S
24 Kovacs G, Herve P, Barbera JA. et al. An official European Respiratory Society statement: pulmonary haemodynamics during exercise. Eur Respir J 2017; 50
25 Ho JE, Zern EK, Lau ES. et al. Exercise Pulmonary Hypertension Predicts Clinical Outcomes in Patients With Dyspnea on Effort. J Am Coll Cardiol 2020; 75: 17-26
26 Kovacs G, Dumitrescu D, Barner A. et al. Definition, clinical classification and initial diagnosis of pulmonary hypertension: Updated recommendations from the Cologne Consensus Conference 2018. Int J Cardiol 2018; 272S: 11-19
27 Frost A, Badesch D, Gibbs JSR. et al. Diagnosis of pulmonary hypertension. Eur Respir J 2019; 53
28 Brown LM, Chen H, Halpern S. et al. Delay in recognition of pulmonary arterial hypertension: factors identified from the REVEAL Registry. Chest 2011; 140: 19-26
29 Kovacs G, Avian A, Foris V. et al. Use of ECG and Other Simple Non-Invasive Tools to Assess Pulmonary Hypertension. PloS One 2016; 11: e0168706
30 Olsson KM, Nickel NP, Tongers J. et al. Atrial flutter and fibrillation in patients with pulmonary hypertension. Int J Cardiol; 2012 http://view.ncbi.nlm.nih.gov/pubmed/22727973
31 Rich S, Dantzker DR, Ayres SM. et al. Primary pulmonary hypertension. A national prospective study. Ann Intern Med 1987; 107: 216-223
32 Milne ENC. Forgotten gold in diagnosing pulmonary hypertension: the plain chest radiograph. Radiogr Rev Publ Radiol Soc N Am Inc 2012; 32: 1085-1087
33 Meyer FJ, Ewert R, Hoeper MM. et al. Peripheral airway obstruction in primary pulmonary hypertension. Thorax 2002; 57: 473-476
34 Nathan SD, Barbera JA, Gaine SP. et al. Pulmonary hypertension in chronic lung disease and hypoxia. Eur Respir J 2019; 53
35 Trip P, Nossent EJ, de Man FS. et al. Severely reduced diffusion capacity in idiopathic pulmonary arterial hypertension: patient characteristics and treatment responses. Eur Respir J 2013; 42: 1575-1585
36 Mecoli CA, Shah AA, Boin F. et al. Vascular complications in systemic sclerosis: a prospective cohort study. Clin Rheumatol 2018; 37: 2429-2437
37 Rose L, Prins KW, Archer SL. et al. Survival in pulmonary hypertension due to chronic lung disease: Influence of low diffusion capacity of the lungs for carbon monoxide. J Heart Lung Transplant Off Publ Int Soc Heart Transplant 2019; 38: 145-155
38 Hoeper MM, Pletz MW, Golpon H. et al. Prognostic value of blood gas analyses in patients with idiopathic pulmonary arterial hypertension. Eur Respir J 2007; 29: 944-450 [Epub 2007 Feb 14. PMID: 17301100]
39 Stadler S, Mergenthaler N, Lange TJ. The prognostic value of DLCO and pulmonary blood flow in patients with pulmonary hypertension. Pulm Circ 2019; 9: 2045894019894531
40 Olsson KM, Sommer L, Fuge J. et al. Capillary pCO2 helps distinguishing idiopathic pulmonary arterial hypertension from pulmonary hypertension due to heart failure with preserved ejection fraction. Respir Res 2015; 16: 34
41 Held M, Walthelm J, Baron S. et al. Functional impact of pulmonary hypertension due to hypoventilation and changes under noninvasive ventilation. Eur Respir J 2014; 43: 156-165
42 Jilwan FN, Escourrou P, Garcia G. et al. High occurrence of hypoxemic sleep respiratory disorders in precapillary pulmonary hypertension and mechanisms. Chest 2013; 143: 47-55
43 Ulrich S, Hasler ED, Saxer S. et al. Effect of breathing oxygen-enriched air on exercise performance in patients with precapillary pulmonary hypertension: randomized, sham-controlled cross-over trial. Eur Heart J 2017; 38: 1159-1168
44 Ulrich S, Saxer S, Hasler ED. et al. Effect of domiciliary oxygen therapy on exercise capacity and quality of life in patients with pulmonary arterial or chronic thromboembolic pulmonary hypertension: a randomised, placebo-controlled trial. Eur Respir J 2019; 54
45 Thakkar V, Stevens W, Prior D. et al. The inclusion of N-terminal pro-brain natriuretic peptide in a sensitive screening strategy for systemic sclerosis-related pulmonary arterial hypertension: a cohort study. Arthritis Res Ther 2013; 15: R193
46 Leuchte HH, Baumgartner RA, Nounou ME. et al. Brain natriuretic peptide is a prognostic parameter in chronic lung disease. Am J Respir Crit Care Med 2006; 173: 744-750
47 Boucly A, Weatherald J, Savale L. et al. Risk assessment, prognosis and guideline implementation in pulmonary arterial hypertension. Eur Respir J 2017; 50
48 Lange TJ, Baumgartner S, Arzt M. et al. Qualitative echocardiography parameters for prediction of pulmonary hypertension. Int J Clin Pract Suppl 2013; 5-12
49 Held M, Grün M, Holl R. et al. Cardiopulmonary exercise testing to detect chronic thromboembolic pulmonary hypertension in patients with normal echocardiography. Respir Int Rev Thorac Dis 2014; 87: 379-387
50 Held M, Kolb P, Grün M. et al. Functional Characterization of Patients with Chronic Thromboembolic Disease. Respir Int Rev Thorac Dis 2016; 91: 503-509
51 Vitarelli A, Mangieri E, Terzano C. et al. Three-dimensional echocardiography and 2D-3D speckle-tracking imaging in chronic pulmonary hypertension: diagnostic accuracy in detecting hemodynamic signs of right ventricular (RV) failure. J Am Heart Assoc 2015; 4: e001584
52 Lange TJ, Dornia C, Stiefel J. et al. Increased pulmonary artery diameter on chest computed tomography can predict borderline pulmonary hypertension. Pulm Circ 2013; 3: 363-368
53 Dornia C, Lange TJ, Behrens G. et al. Multidetector Computed Tomography for Detection and Characterization of Pulmonary Hypertension in Consideration of WHO Classification. J Comput Assist Tomogr 2012; 36: 175-180
54 Tan RT, Kuzo R, Goodman LR. et al. Utility of CT scan evaluation for predicting pulmonary hypertension in patients with parenchymal lung disease. Medical College of Wisconsin Lung Transplant Group. Chest 1998; 113: 1250-1256
55 Pienn M, Kovacs G, Tscherner M. et al. Non-invasive determination of pulmonary hypertension with dynamic contrast-enhanced computed tomography: a pilot study. Eur Radiol 2014; 24: 668-676
56 Pienn M, Kovacs G, Tscherner M. et al. Determination of cardiac output with dynamic contrast-enhanced computed tomography. Int J Cardiovasc Imaging 2013; 29: 1871-1878
57 Aviram G, Rozenbaum Z, Ziv-Baran T. et al. Identification of Pulmonary Hypertension Caused by Left-Sided Heart Disease (World Health Organization Group 2) Based on Cardiac Chamber Volumes Derived From Chest CT Imaging. Chest 2017; 152: 792-799
58 Masy M, Giordano J, Petyt G. et al. Dual-energy CT (DECT) lung perfusion in pulmonary hypertension: concordance rate with V/Q scintigraphy in diagnosing chronic thromboembolic pulmonary hypertension (CTEPH). Eur Radiol 2018; 28: 5100-5110
59 Ogo T, Fukuda T, Tsuji A. et al. Efficacy and safety of balloon pulmonary angioplasty for chronic thromboembolic pulmonary hypertension guided by cone-beam computed tomography and electrocardiogram-gated area detector computed tomography. Eur J Radiol 2017; 89: 270-276
60 Fukuda T, Ogo T, Nakanishi N. et al. Evaluation of organized thrombus in distal pulmonary arteries in patients with chronic thromboembolic pulmonary hypertension using cone-beam computed tomography. Jpn J Radiol 2016; 34: 423-431
61 Wilkens H, Konstantinides S, Lang IM. et al. Chronic thromboembolic pulmonary hypertension (CTEPH): Updated Recommendations from the Cologne Consensus Conference 2018. Int J Cardiol 2018; 272S: 69-78
62 Ali N, Loughborough WW, Rodrigues JCL. et al. Computed tomographic and clinical features of pulmonary veno-occlusive disease: raising the radiologist’s awareness. Clin Radiol 2019; 74: 655-662
63 Altschul E, Remy-Jardin M, Machnicki S. et al. Imaging of Pulmonary Hypertension: Pictorial Essay. Chest 2019; 156: 211-227
64 Kasai H, Tanabe N, Fujimoto K. et al. Mosaic attenuation pattern in non-contrast computed tomography for the assessment of pulmonary perfusion in chronic thromboembolic pulmonary hypertension. Respir Investig 2017; 55: 300-307
65 Galiè N, Saia F, Palazzini M. et al. Left Main Coronary Artery Compression in Patients With Pulmonary Arterial Hypertension and Angina. J Am Coll Cardiol 2017; 69: 2808-2817
66 Sugiura T, Tanabe N, Matsuura Y. et al. Role of 320-slice CT imaging in the diagnostic workup of patients with chronic thromboembolic pulmonary hypertension. Chest 2013; 143: 1070-1077
67 Tunariu N, Gibbs SJR, Win Z. et al. 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; 48: 680-684
68 Derlin T, Kelting C, Hueper K. et al. Quantitation of Perfused Lung Volume Using Hybrid SPECT/CT Allows Refining the Assessment of Lung Perfusion and Estimating Disease Extent in Chronic Thromboembolic Pulmonary Hypertension. Clin Nucl Med 2018; 43: e170-e177
69 Hinrichs JB, Marquardt S, von Falck C. et al. Comparison of C-arm Computed Tomography and Digital Subtraction Angiography in Patients with Chronic Thromboembolic Pulmonary Hypertension. Cardiovasc Intervent Radiol 2016; 39: 53-63
70 Alduraibi A, Fathala A. Normal ventilation/perfusion lung scan in patients with extensive chronic thromboembolism pulmonary hypertension: A case report. Radiol Case Rep 2019; 14: 510-513
71 Bajc M, Schümichen C, Grüning T. et al. EANM guideline for ventilation/perfusion single-photon emission computed tomography (SPECT) for diagnosis of pulmonary embolism and beyond. Eur J Nucl Med Mol Imaging 2019; 46: 2429-2451
72 Chan K, Ioannidis S, Coghlan JG. et al. Pulmonary Arterial Hypertension With Abnormal V/Q Single-Photon Emission Computed Tomography. JACC Cardiovasc Imaging 2018; 11: 1487-1493
73 Lahm T, Douglas IS, Archer SL. et al. Assessment of Right Ventricular Function in the Research Setting: Knowledge Gaps and Pathways Forward. An Official American Thoracic Society Research Statement. Am J Respir Crit Care Med 2018; 198: e15-e43
74 Jose A, Kher A, O’Donnell RE. et al. Cardiac magnetic resonance imaging as a prognostic biomarker in treatment-naïve pulmonary hypertension. Eur J Radiol 2020; 123: 108784
75 Lewis RA, Johns CS, Cogliano M. et al. Identification of Cardiac Magnetic Resonance Imaging Thresholds for Risk Stratification in Pulmonary Arterial Hypertension. Am J Respir Crit Care Med 2020; 201: 458-468
76 Rajaram S, Swift AJ, Telfer A. et al. 3D contrast-enhanced lung perfusion MRI is an effective screening tool for chronic thromboembolic pulmonary hypertension: results from the ASPIRE Registry. Thorax 2013; 68: 677-678
77 Johns CS, Swift AJ, Rajaram S. et al. Lung perfusion: MRI vs. SPECT for screening in suspected chronic thromboembolic pulmonary hypertension. J Magn Reson Imaging JMRI 2017; 46: 1693-1697
78 Maschke SK, Winther HMB, Meine T. et al. Evaluation of a newly developed 2D parametric parenchymal blood flow technique with an automated vessel suppression algorithm in patients with chronic thromboembolic pulmonary hypertension undergoing balloon pulmonary angioplasty. Clin Radiol 2019; 74: 437-444
79 Meyer FJ, Borst MM, Buschmann H-C. et al. Exercise Testing in Respiratory Medicine - DGP Recommendations. Pneumol Stuttg Ger 2018; 72: 687-731
80 ATS Committee on Proficiency Standards for Clinical Pulmonary Function Laboratories. ATS statement: guidelines for the six-minute walk test. Am J Respir Crit Care Med 2002; 166: 111-117
81 Lee W-TN, Peacock AJ, Johnson MK. The role of per cent predicted 6-min walk distance in pulmonary arterial hypertension. Eur Respir J 2010; 36: 1294-1301
82 Lange TJ, Keller A, Arzt M. et al. Six-minute walk distance target in elderly patients with idiopathic pulmonary arterial hypertension - consideration of predicted values. Int J Clin Pract 2014; 68: 543-550
83 Miyamoto S, Nagaya N, Satoh T. et al. Clinical correlates and prognostic significance of six-minute walk test in patients with primary pulmonary hypertension. Comparison with cardiopulmonary exercise testing. Am J Respir Crit Care Med 2000; 161: 487-492
84 Zelniker TA, Huscher D, Vonk-Noordegraaf A. et al. The 6MWT as a prognostic tool in pulmonary arterial hypertension: results from the COMPERA registry. Clin Res Cardiol Off J Ger Card Soc 2018; 107: 460-470
85 Farber HW, Miller DP, McGoon MD. et al. Predicting outcomes in pulmonary arterial hypertension based on the 6-minute walk distance. J Heart Lung Transplant Off Publ Int Soc Heart Transplant 2015; 34: 362-368
86 Sitbon O, Humbert M, Nunes H. et al. Long-term intravenous epoprostenol infusion in primary pulmonary hypertension: prognostic factors and survival. J Am Coll Cardiol 2002; 40: 780-788
87 Gaine S, Simonneau G. The need to move from 6-minute walk distance to outcome trials in pulmonary arterial hypertension. Eur Respir Rev Off J Eur Respir Soc 2013; 22: 487-494
88 Farina S, Correale M, Bruno N. et al. The role of cardiopulmonary exercise tests in pulmonary arterial hypertension. Eur Respir Rev Off J Eur Respir Soc 2018; 27
89 Radtke T, Vogiatzis I, Urquhart DS. et al. Standardisation of cardiopulmonary exercise testing in chronic lung diseases: summary of key findings from the ERS task force. Eur Respir J 2019; 54
90 Theodore J, Robin ED, Morris AJ. et al. Augmented ventilatory response to exercise in pulmonary hypertension. Chest 1986; 89: 39-44
91 Reybrouck T, Mertens L, Schulze-Neick I. et al. Ventilatory inefficiency for carbon dioxide during exercise in patients with pulmonary hypertension. Clin Physiol Oxf Engl 1998; 18: 337-344
92 Ting H, Sun XG, Chuang ML. et al. A noninvasive assessment of pulmonary perfusion abnormality in patients with primary pulmonary hypertension. Chest 2001; 119: 824-832
93 Sun XG, Hansen JE, Oudiz RJ. et al. Exercise pathophysiology in patients with primary pulmonary hypertension. Circulation 2001; 104: 429-435
94 Wensel R, Opitz CF, Ewert R. et al. Effects of iloprost inhalation on exercise capacity and ventilatory efficiency in patients with primary pulmonary hypertension. Circulation 2000; 101: 2388-2392
95 Wax D, Garofano R, Barst RJ. Effects of long-term infusion of prostacyclin on exercise performance in patients with primary pulmonary hypertension. Chest 1999; 116: 914-920
96 Puente-Maestu L, Palange P, Casaburi R. et al. Use of exercise testing in the evaluation of interventional efficacy: an official ERS statement. Eur Respir J 2016; 47: 429-460
97 Meyer FJ, Lossnitzer D, Kristen AV. et al. Respiratory muscle dysfunction in idiopathic pulmonary arterial hypertension. Eur Respir J 2005; 25: 125-130
98 Boucly A, Morélot-Panzini C, Garcia G. et al. Intensity and quality of exertional dyspnoea in patients with stable pulmonary hypertension. Eur Respir J 2020; 55
99 Richter MJ, Tiede H, Morty RE. et al. The prognostic significance of inspiratory capacity in pulmonary arterial hypertension. Respir Int Rev Thorac Dis 2014; 88: 24-30
100 Deboeck G, Niset G, Lamotte M. et al. Exercise testing in pulmonary arterial hypertension and in chronic heart failure. Eur Respir J 2004; 23: 747-751
101 Chen Y-J, Tu H-P, Lee C-L. et al. Comprehensive Exercise Capacity and Quality of Life Assessments Predict Mortality in Patients with Pulmonary Arterial Hypertension. Acta Cardiol Sin 2019; 35: 55-64
102 Wensel R, Francis DP, Meyer FJ. et al. Incremental prognostic value of cardiopulmonary exercise testing and resting haemodynamics in pulmonary arterial hypertension. Int J Cardiol 2013; 167: 1193-1198
103 Arena R, Lavie CJ, Milani RV. et al. Cardiopulmonary exercise testing in patients with pulmonary arterial hypertension: an evidence-based review. J Heart Lung Transplant Off Publ Int Soc Heart Transplant 2010; 29: 159-173
104 Leuchte HH, Ten FreyhausH, Gall H. et al. Risk stratification strategy and assessment of disease progression in patients with pulmonary arterial hypertension: Updated Recommendations from the Cologne Consensus Conference 2018. Int J Cardiol 2018;
105 Badagliacca R, Papa S, Poscia R. et al. The added value of cardiopulmonary exercise testing in the follow-up of pulmonary arterial hypertension. J Heart Lung Transplant Off Publ Int Soc Heart Transplant 2019; 38: 306-314
106 Peacock A, Naeije R, Galié N. et al. End points in pulmonary arterial hypertension: the way forward. Eur Respir J 2004; 23: 947-953
107 Mainguy V, Malenfant S, Neyron A-S. et al. Repeatability and responsiveness of exercise tests in pulmonary arterial hypertension. Eur Respir J 2013; 42: 425-434
108 Hansen JE, Sun X-G, Yasunobu Y. et al. Reproducibility of cardiopulmonary exercise measurements in patients with pulmonary arterial hypertension. Chest 2004; 126: 816-824
109 Oudiz RJ, Barst RJ, Hansen JE. et al. Cardiopulmonary exercise testing and six-minute walk correlations in pulmonary arterial hypertension. Am J Cardiol 2006; 97: 123-126
110 Yasunobu Y, Oudiz RJ, Sun X-G. et al. End-tidal PCO2 abnormality and exercise limitation in patients with primary pulmonary hypertension. Chest 2005; 127: 1637-1646
111 Dumitrescu D, Oudiz RJ, Karpouzas G. et al. Developing pulmonary vasculopathy in systemic sclerosis, detected with non-invasive cardiopulmonary exercise testing. PloS One 2010; 5: e14293
112 Jiang R, Liu H, Pudasaini B. et al. Characteristics of cardiopulmonary exercise testing of patients with borderline mean pulmonary artery pressure. Clin Respir J 2019; 13: 148-158
113 Santaniello A, Casella R, Vicenzi M. et al. Cardiopulmonary exercise testing in a combined screening approach to individuate pulmonary arterial hypertension in systemic sclerosis. Rheumatol Oxf Engl 2019;
114 Boerrigter BG, Bogaard HJ, Trip P. et al. Ventilatory and cardiocirculatory exercise profiles in COPD: the role of pulmonary hypertension. Chest 2012; 142: 1166-1174
115 Scheidl SJ, Englisch C, Kovacs G. et al. Diagnosis of CTEPH versus IPAH using capillary to end-tidal carbon dioxide gradients. Eur Respir J 2012; 39: 119-124
116 Weatherald J, Farina S, Bruno N. et al. Cardiopulmonary Exercise Testing in Pulmonary Hypertension. Ann Am Thorac Soc 2017; 14 (Suppl. 01) S84-S92
117 Yang HS, Mookadam F, Warsame TA. et al. Evaluation of right ventricular global and regional function during stress echocardiography using novel velocity vector imaging. Eur J Echocardiogr J Work Group Echocardiogr Eur Soc Cardiol 2010; 11: 157-164
118 Lopes LR, Loureiro MJ, Miranda R. et al. The usefulness of contrast during exercise echocardiography for the assessment of systolic pulmonary pressure. Cardiovasc Ultrasound 2008; 6: 51
119 Bossone E, D’Andrea A, D’Alto M. et al. Echocardiography in pulmonary arterial hypertension: from diagnosis to prognosis. J Am Soc Echocardiogr Off Publ Am Soc Echocardiogr 2013; 26: 1-14
120 Liu B-Y, Wu W-C, Zeng Q-X. et al. Two-dimensional speckle tracking echocardiography assessed right ventricular function and exercise capacity in pre-capillary pulmonary hypertension. Int J Cardiovasc Imaging 2019; 35: 1499-1508
121 El-Yafawi R, Rancourt D, Hacobian M. et al. Pulmonary hypertension subjects exhibit right ventricular transient exertional dilation during supine exercise stress echocardiography. Pulm Circ 2019; 9: 2045894019851904
122 Caravita S, Yerly P, Baratto C. et al. Noninvasive versus invasive pressure-flow relationship of the pulmonary circulation: bias and error. Eur Respir J 2019; 54
123 Grünig E, Tiede H, Enyimayew EO. et al. Assessment and prognostic relevance of right ventricular contractile reserve in patients with severe pulmonary hypertension. Circulation 2013; 128: 2005-2015
124 Korff S, Enders-Gier P, Uhlmann L. et al. Systolic pulmonary artery pressure assessed during routine exercise Doppler echocardiography: insights of a real-world setting in patients with elevated pulmonary pressures. Int J Cardiovasc Imaging 2018; 34: 1215-1225
125 Fischer L, Benjamin N, Blank N. et al. Right heart size and function significantly correlate in patients with pulmonary arterial hypertension - a cross-sectional study. Respir Res 2018; 19: 216
126 Gorter TM, Obokata M, Reddy YNV. et al. Exercise unmasks distinct pathophysiologic features in heart failure with preserved ejection fraction and pulmonary vascular disease. Eur Heart J 2018; 39: 2825-2835
127 Suzuki K, Hirano Y, Yamada H. et al. Practical guidance for the implementation of stress echocardiography. J Echocardiogr 2018; 16: 105-129
128 Nanayakkara S, Kaye DM, Marwick TH. Resting and Exercise Doppler Hemodynamics: How and Why?. Heart Fail Clin 2019; 15: 229-239
129 Ferrara F, Zhou X, Gargani L. et al. Echocardiography in Pulmonary Arterial Hypertension. Curr Cardiol Rep 2019; 21: 22
130 Hoeper MM, Lee SH, Voswinckel R. et al. Complications of right heart catheterization procedures in patients with pulmonary hypertension in experienced centers. J Am Coll Cardiol 2006; 48: 2546-2552
131 Vachiéry J-L, Tedford RJ, Rosenkranz S. et al. Pulmonary hypertension due to left heart disease. Eur Respir J 2019; 53
132 Kovacs G, Avian A, Olschewski A. et al. Zero reference level for right heart catheterisation. Eur Respir J 2013; 42: 1586-1594
133 Kovacs G, Avian A, Pienn M. et al. Reading pulmonary vascular pressure tracings. How to handle the problems of zero leveling and respiratory swings. Am J Respir Crit Care Med 2014; 190: 252-257
134 Jing Z-C, Jiang X, Han Z-Y. et al. Iloprost for pulmonary vasodilator testing in idiopathic pulmonary arterial hypertension. Eur Respir J 2009; 33: 1354-1360
135 Opitz CF, Rubin LJ. Acute vasodilator testing in idiopathic pulmonary arterial hypertension: must we take NO for the answer?. Eur Respir J 2009; 33: 1247-1249
136 Montani D, Savale L, Natali D. et al. Long-term response to calcium-channel blockers in non-idiopathic pulmonary arterial hypertension. Eur Heart J 2010; 31: 1898-1907
137 Leuchte HH, Baezner C, Baumgartner RA. et al. Residual pulmonary vasodilative reserve predicts outcome in idiopathic pulmonary hypertension. Heart Br Card Soc 2015; 101: 972-976
138 Hoeper MM, Maier R, Tongers J. et al. Determination of cardiac output by the Fick method, thermodilution, and acetylene rebreathing in pulmonary hypertension. Am J Respir Crit Care Med 1999; 160: 535-541
139 Narang N, Thibodeau JT, Levine BD. et al. Inaccuracy of estimated resting oxygen uptake in the clinical setting. Circulation 2014; 129: 203-210
140 Held M, Linke M, Jany B. Echocardiography and right heart catheterization in pulmonal hypertension. Dtsch Med Wochenschr 1946 2014; 139: 1511-1517
141 McCabe C, Deboeck G, Harvey I. et al. Inefficient exercise gas exchange identifies pulmonary hypertension in chronic thromboembolic obstruction following pulmonary embolism. Thromb Res 2013; 132: 659-665