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Semin Respir Crit Care Med 2023; 44(06): 728-737
DOI: 10.1055/s-0043-1770116
Review Article

The Diagnostic Approach to Pulmonary Hypertension

Adam Torbicki
1   Department of Pulmonary Circulation, Thromboembolic Diseases and Cardiology, Centre for Postgraduate Medical Education at ECZ-Otwock, Otwock, Poland
,
Marcin Kurzyna
1   Department of Pulmonary Circulation, Thromboembolic Diseases and Cardiology, Centre for Postgraduate Medical Education at ECZ-Otwock, Otwock, Poland
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Abstract

The clinical presentation of pulmonary hypertension (PH) is nonspecific, resulting in significant delays in its detection. In the majority of cases, PH is a marker of the severity of other cardiopulmonary diseases. Differential diagnosis aimed at the early identification of patients with pulmonary arterial hypertension (PAH) and chronic thromboembolic pulmonary hypertension (CTEPH) who do require specific and complex therapies is as important as PH detection itself. Despite all efforts aimed at the noninvasive assessment of pulmonary arterial pressure, the formal confirmation of PH still requires catheterization of the right heart and pulmonary artery. The current document will give an overview of strategies aimed at the early diagnosis of PAH and CTEPH, while avoiding their overdiagnosis. It is not intended to be a replica of the recently published European Society of Cardiology (ESC) and European Respiratory Society (ERS) Guidelines on Diagnosis and Treatment of Pulmonary Hypertension, freely available at the Web sites of both societies. While promoting guidelines' recommendations, including those on new definitions of PH, we will try to bring them closer to everyday clinical practice, benefiting from our personal experience in managing patients with suspected PH.

Keywords

pulmonary hypertension - diagnosis - screening - guidelines


Publication History

Article published online:
24 July 2023

© 2023. Thieme. All rights reserved.

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  • References

  • 1 Hoeper MM, Humbert M, Souza R. et al. A global view of pulmonary hypertension. Lancet Respir Med 2016; 4 (04) 306-322
    CrossrefPubMedGoogle Scholar
  • 2 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
    CrossrefPubMedGoogle Scholar
  • 3 Humbert M, Kovacs G, Hoeper MM. et al. 2022 ESC/ERS guidelines for the diagnosis and treatment of pulmonary hypertension. Eur Heart J 2022; 43 (38) 3618-3731
    CrossrefPubMedGoogle Scholar
  • 4 Frost A, Badesch D, Gibbs JSR. et al. Diagnosis of pulmonary hypertension. Eur Respir J 2019; 53 (01) 1801904
    CrossrefPubMedGoogle Scholar
  • 5 Armstrong I, Billings C, Kiely DG. et al. The patient experience of pulmonary hypertension: a large cross-sectional study of UK patients. BMC Pulm Med 2019; 19 (01) 67
    CrossrefPubMedGoogle Scholar
  • 6 Khou V, Anderson JJ, Strange G. et al. Diagnostic delay in pulmonary arterial hypertension: insights from the Australian and New Zealand pulmonary hypertension registry. Respirology 2020; 25 (08) 863-871
    CrossrefPubMedGoogle Scholar
  • 7 Rich S, Dantzker DR, Ayres SM. et al. Primary pulmonary hypertension. A national prospective study. Ann Intern Med 1987; 107 (02) 216-223
    CrossrefPubMedGoogle Scholar
  • 8 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 (12) e0168706
    CrossrefPubMedGoogle Scholar
  • 9 Remy-Jardin M, Ryerson CJ, Schiebler ML. et al. Imaging of pulmonary hypertension in adults: a position paper from the Fleischner Society. Eur Respir J 2021; 57 (01) 2004455
    CrossrefPubMedGoogle Scholar
  • 10 Sun XG, Hansen JE, Oudiz RJ, Wasserman K. Pulmonary function in primary pulmonary hypertension. J Am Coll Cardiol 2003; 41 (06) 1028-1035
    CrossrefPubMedGoogle Scholar
  • 11 Olsson KM, Sommer L, Fuge J, Welte T, Hoeper MM. Capillary pCO2 helps distinguishing idiopathic pulmonary arterial hypertension from pulmonary hypertension due to heart failure with preserved ejection fraction. Respir Res 2015; 16 (01) 34
    CrossrefPubMedGoogle Scholar
  • 12 Mak SM, Strickland N, Gopalan D. Complications of pulmonary hypertension: a pictorial review. Br J Radiol 2017; 90 (1070): 20160745
    CrossrefPubMedGoogle Scholar
  • 13 Rudski LG, Lai WW, Afilalo J. et al. Guidelines for the echocardiographic assessment of the right heart in adults: a report from the American Society of Echocardiography endorsed by the European Association of Echocardiography, a registered branch of the European Society of Cardiology, and the Canadian Society of Echocardiography. J Am Soc Echocardiogr 2010; 23 (07) 685-713 , quiz 786–788
    CrossrefPubMedGoogle Scholar
  • 14 D'Alto M, Romeo E, Argiento P. et al. Accuracy and precision of echocardiography versus right heart catheterization for the assessment of pulmonary hypertension. Int J Cardiol 2013; 168 (04) 4058-4062
    CrossrefPubMedGoogle Scholar
  • 15 Coghlan JG, Denton CP, Grünig E. et al; DETECT Study Group. Evidence-based detection of pulmonary arterial hypertension in systemic sclerosis: the DETECT study. Ann Rheum Dis 2014; 73 (07) 1340-1349
    CrossrefPubMedGoogle Scholar
  • 16 Chemla D, Hervé P. Estimation of mean pulmonary artery pressure: simpler than expected. Chest 2008; 133 (03) 592-593
    CrossrefPubMedGoogle Scholar
  • 17 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 (13) 1240-1248
    CrossrefPubMedGoogle Scholar
  • 18 Pieske B, Tschöpe C, de Boer RA. et al. How to diagnose heart failure with preserved ejection fraction: the HFA-PEFF diagnostic algorithm: a consensus recommendation from the Heart Failure Association (HFA) of the European Society of Cardiology (ESC). Eur J Heart Fail 2020; 22 (03) 391-412
    CrossrefPubMedGoogle Scholar
  • 19 Olschewski H. The challenge to decide between pulmonary hypertension due to chronic lung disease and PAH with chronic lung disease. Diagnostics (Basel) 2021; 11 (02) 311
    CrossrefPubMedGoogle Scholar
  • 20 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 (12) 2546-2552
    CrossrefPubMedGoogle Scholar
  • 21 Opotowsky AR, Hess E, Maron BA. et al. Thermodilution vs estimated Fick cardiac output measurement in clinical practice: an analysis of mortality from the Veterans Affairs Clinical Assessment, Reporting, and Tracking (VA CART) Program and Vanderbilt University. JAMA Cardiol 2017; 2 (10) 1090-1099
    CrossrefPubMedGoogle Scholar
  • 22 Kovacs G, Douschan P, Maron BA, Condliffe R, Olschewski H. Mildly increased pulmonary arterial pressure: a new disease entity or just a marker of poor prognosis?. Eur J Heart Fail 2019; 21 (09) 1057-1061
    CrossrefPubMedGoogle Scholar
  • 23 Delcroix M, Torbicki A, Gopalan D. et al. ERS statement on chronic thromboembolic pulmonary hypertension. Eur Respir J 2021; 57 (06) 2002828
    CrossrefPubMedGoogle Scholar
  • 24 Kovacs G, Herve P, Olschewski H. PEX-NET Clinical Research Collaboration. The pulmonary haemodynamics during exercise - research network (PEX-NET) ERS Clinical Research Collaboration: investigating the prognostic relevance of exercise haemodynamics. Eur Respir J 2019; 53 (04) 1900458
    CrossrefPubMedGoogle Scholar
  • 25 Sun XG, Hansen JE, Oudiz RJ, Wasserman K. Exercise pathophysiology in patients with primary pulmonary hypertension. Circulation 2001; 104 (04) 429-435
    CrossrefPubMedGoogle Scholar
  • 26 Caravita S, Faini A, Deboeck G. et al. Pulmonary hypertension and ventilation during exercise: role of the pre-capillary component. J Heart Lung Transplant 2017; 36 (07) 754-762
    CrossrefPubMedGoogle Scholar
  • 27 Baigent C, Windecker S, Andreini D. et al; Task Force for the management of COVID-19 of the European Society of Cardiology. European Society of Cardiology guidance for the diagnosis and management of cardiovascular disease during the COVID-19 pandemic: part 1-epidemiology, pathophysiology, and diagnosis. Cardiovasc Res 2022; 118 (06) 1385-1412
    CrossrefPubMedGoogle Scholar
  • 28 Swift AJ, Dwivedi K, Johns C. et al. Diagnostic accuracy of CT pulmonary angiography in suspected pulmonary hypertension. Eur Radiol 2020; 30 (09) 4918-4929
    CrossrefPubMedGoogle Scholar
  • 29 Tunariu N, Gibbs SJ, 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 (05) 680-684
    CrossrefPubMedGoogle Scholar
  • 30 Ende-Verhaar YM, Meijboom LJ, Kroft LJM. et al. Usefulness of standard computed tomography pulmonary angiography performed for acute pulmonary embolism for identification of chronic thromboembolic pulmonary hypertension: results of the InShape III study. J Heart Lung Transplant 2019; 38 (07) 731-738
    CrossrefPubMedGoogle Scholar
  • 31 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 (12) 5100-5110
    CrossrefPubMedGoogle Scholar
  • 32 He J, Fang W, Lv B. et al. Diagnosis of chronic thromboembolic pulmonary hypertension: comparison of ventilation/perfusion scanning and multidetector computed tomography pulmonary angiography with pulmonary angiography. Nucl Med Commun 2012; 33 (05) 459-463
    CrossrefPubMedGoogle Scholar
  • 33 Seferian A, Helal B, Jaïs X. et al. Ventilation/perfusion lung scan in pulmonary veno-occlusive disease. Eur Respir J 2012; 40 (01) 75-83
    CrossrefPubMedGoogle Scholar
  • 34 Lasch F, Karch A, Koch A. et al. Comparison of MRI and VQ-SPECT as a screening test for patients with suspected CTEPH: CHANGE-MRI study design and rationale. Front Cardiovasc Med 2020; 7: 51
    CrossrefPubMedGoogle Scholar
  • 35 Klok FA, Surie S, Kempf T. et al. A simple non-invasive diagnostic algorithm for ruling out chronic thromboembolic pulmonary hypertension in patients after acute pulmonary embolism. Thromb Res 2011; 128 (01) 21-26
    CrossrefPubMedGoogle Scholar
  • 36 Eyries M, Montani D, Girerd B. et al. EIF2AK4 mutations cause pulmonary veno-occlusive disease, a recessive form of pulmonary hypertension. Nat Genet 2014; 46 (01) 65-69
    CrossrefPubMedGoogle Scholar
  • 37 Montani D, Girerd B, Jaïs X. et al. Screening for pulmonary arterial hypertension in adults carrying a BMPR2 mutation. Eur Respir J 2021; 58 (01) 2004229
    CrossrefPubMedGoogle Scholar
  • 38 Raevens S, Colle I, Reyntjens K. et al. Echocardiography for the detection of portopulmonary hypertension in liver transplant candidates: an analysis of cutoff values. Liver Transpl 2013; 19 (06) 602-610
    CrossrefPubMedGoogle Scholar
  • 39 Nijkeuter M, Hovens MM, Davidson BL, Huisman MV. Resolution of thromboemboli in patients with acute pulmonary embolism: a systematic review. Chest 2006; 129 (01) 192-197
    CrossrefPubMedGoogle Scholar
  • 40 Konstantinides SV, Meyer G, Becattini C. et al. 2019 ESC Guidelines for the diagnosis and management of acute pulmonary embolism developed in collaboration with the European Respiratory Society (ERS): the Task Force for the Diagnosis and management of acute pulmonary embolism of the European Society of Cardiology (ESC). Eur Heart J 2020; 41 (04) 543-603
    CrossrefPubMedGoogle Scholar
  • 41 Liu CM, Shih ESC, Chen JY. et al. Artificial intelligence-enabled electrocardiogram improves the diagnosis and prediction of mortality in patients with pulmonary hypertension. JACC Asia 2022; 2 (03) 258-270
    CrossrefPubMedGoogle Scholar
  • 42 Dubrock HM, Wagner E, Attia ZI. Early detection of pulmonary arterial hypertension using a pulmonary hypertension electrocardiogram algorithm. Paper presented at: ATS Annual Meeting, May 18, 2022. Am J Respir Crit Care Med 2022; 205: A5300
    PubMedGoogle Scholar
  • 43 Reiter G, Reiter U, Kovacs G. et al. Magnetic resonance-derived 3-dimensional blood flow patterns in the main pulmonary artery as a marker of pulmonary hypertension and a measure of elevated mean pulmonary arterial pressure. Circ Cardiovasc Imaging 2008; 1 (01) 23-30
    CrossrefPubMedGoogle Scholar
  • 44 Ramos JG, Wieslander B, Fyrdahl A. et al. Pulmonary hypertension by catheterization is more accurately detected by cardiovascular magnetic resonance 4D-flow than echocardiography. JACC Cardiovasc Imaging 2022
    PubMedGoogle Scholar
  • 45 Gopalan D, Gibbs JSR. From early morphometrics to machine learning - What future for cardiovascular imaging of the pulmonary circulation?. Diagnostics (Basel) 2020; 10 (12) 1004
    CrossrefPubMedGoogle Scholar
  • 46 Dwivedi K, Sharkey M, Condliffe R. et al. Pulmonary hypertension in association with lung disease: Quantitative CT and artificial intelligence to the rescue? State-of-the-art review. Diagnostics (Basel) 2021; 11 (04) 679
    CrossrefPubMedGoogle Scholar
  • 47 Kedzierski P, Torbicki A. Precision medicine: the future of diagnostic approach to pulmonary hypertension?. Anatol J Cardiol 2019; 22 (04) 168-171
    PubMedGoogle Scholar
  • 48 Nakhleh MK, Haick H, Humbert M, Cohen-Kaminsky S. Volatolomics of breath as an emerging frontier in pulmonary arterial hypertension. Eur Respir J 2017; 49 (02) 1601897
    CrossrefPubMedGoogle Scholar
  • 49 Rhodes CJ, Ghataorhe P, Wharton J. et al. Plasma metabolomics implicates modified transfer RNAs and altered bioenergetics in the outcomes of pulmonary arterial hypertension. Circulation 2017; 135 (05) 460-475
    CrossrefPubMedGoogle Scholar
  • 50 Lee MH, Menezes TCF, Reisz JA, Ferreira EVM, Graham BB, Oliveira RKF. Exercise metabolomics in pulmonary arterial hypertension: where pulmonary vascular metabolism meets exercise physiology. Front Physiol 2022; 13: 963881
    CrossrefPubMedGoogle Scholar
  • 51 Winter P, Carusi A. Professional expectations and patient expectations concerning the development of Artificial Intelligence (AI) for the early diagnosis of Pulmonary Hypertension (PH). J Responsib Technol 2022; DOI: 10.1016/j.jrt.2022.100052.
    CrossrefPubMedGoogle Scholar