A modern perspective on pulmonary hypertension phenotypes: a literature review
https://doi.org/10.15829/1560-4071-2025-6701
EDN: IUHKND
Abstract
Significant progress has been made in recent years in understanding the pathogenesis of various types of pulmonary hypertension (PH), as well as in improving diagnostic approaches and treatment algorithms. The increasing prevalence of PH worldwide is associated with demographic changes, particularly the increasing proportion of the elderly population and lifestyle changes. The past three decades have been characterized by a dramatic shift in the phenotype of patients with pulmonary arterial hypertension (PAH), driven by population aging and the diagnosis being confirmed in older age groups with complex comorbidity status. Despite its relative rarity, PAH represents a significant healthcare problem worldwide, as its incidence and prevalence of PAH are increasing. This, in turn, may indicate increased awareness and timely diagnosis of the disease, which is associated with a decrease in global mortality from PAH.
This review highlights current approaches to classifying and phenotyping patients with PH, outlines global trends in disease prevalence and prognosis, and discusses new trends in the development of personalized treatment for various phenotypes of patients with PAH.
About the Author
I. N. Lyapina
Research Institute for Complex Issues of Cardiovascular Diseases
Russian Federation
Competing Interests:
Russian Federation
Acad. L.S. Barbarash blvd., 6, Kemerovo, 650002
Competing Interests:
None
References
1. Osokina AK, Rodnenkov OV, Martynyuk TV. Historical milestones in the study of pulmonary hypertension. Terapevticheskii Arkhiv. 2025;97(3):289-95. (In Russ.) doi:10.26442/00403660.2025.03.203137.
2. Avdeev SN, Barbarash OL, Valieva ZS, et al. 2024 Clinical practice guidelines for Pulmonary hypertension, including chronic thromboembolic pulmonary hypertension. Russian Journal of Cardiology. 2024;29(11):6161. (In Russ.) doi:10.15829/1560-4071-2024-6161.
3. Сhazova IE, Martynyuk TV, Shmalts AA, et al. Eurasian guidelines for the diagnosis and treatment of pulmonary hypertension (2023). Eurasian heart journal. 2024;(1):6-85. (In Russ.)
4. 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 Developed by the task force for the diagnosis and treatment of pulmonary hypertension of the European Society of Cardiology (ESC) and the European Respiratory Society (ERS)). Eur Heart J. 2022;43(38):3618-731.
5. Wijeratne DT, Lajkosz K, Brogly SB, et al. Increasing Incidence and Prevalence of World Health Organization Groups 1 to 4 Pulmonary Hypertension: A Population-Based Cohort Study in Ontario, Canada. Circ Cardiovasc Qual Outcomes. 2018;11(2):e003973. doi:10.1161/CIRCOUTCOMES.117.003973.
6. Plotnikova MR, Mustafina IA, Scheckin VS, et al. Phenotypes of Chronic Heart Failure in Patients with Preserved Ejection Fraction. Kardiologiia. 2025;65(10):101-8. (In Russ.) doi:10.18087/cardio.2025.10.n3021.
7. Rich S, Dantzker DR, Ayres SM, et al. Primary pulmonary hypertension. A national prospective study. Ann Intern Med. 1987;107(2):216-23. doi:10.7326/0003-4819-107-2-216.
8. Badesch DB, Raskob GE, Elliott CG, et al. Pulmonary arterial hypertension: baseline characteristics from the REVEAL Registry. Chest. 2010;137(2):376-87. doi:10.1378/chest.09-1140.
9. Hoeper MM, Huscher D, Ghofrani HA, et al. Elderly patients diagnosed with idiopathic pulmonary arterial hypertension: results from the COMPERA registry. Int J Cardiol. 2013;168(2):871-80. doi:10.1016/j.ijcard.2012.10.026.
10. Chazova IE, Martynyuk TV, Valieva ZS, et al. Clinical and Instrumental Characteristics of Newly Diagnosed Patients with Various Forms of Pulmonary Hypertension according to the Russian National Registry. BioMed Research International. 2020:6836973. doi:10.1155/2020/6836973.
11. Huang H, Hu C, Zhang R, et al. Global Burden of Pulmonary Arterial Hypertension and Associated Heart Failure: Global Burden of Disease 2021 Analysis. JACC Heart Fail. 2025;13(10):102385. doi:10.1016/j.jchf.2024.12.005.
12. GBD 2021 Pulmonary Arterial Hypertension Collaborators. Global, regional, and national burden of pulmonary arterial hypertension, 1990-2021: a systematic analysis for the Global Burden of Disease Study 2021. Lancet Respir Med. 2025;13(1):69-79. doi:10.1016/S2213-2600(24)00295-9.
13. Zhang S, Gao L, Li S, et al. Is pulmonary vascular remodeling an intermediate link between hyperglycemia and adverse outcomes in patients with idiopathic pulmonary arterial hypertension? Insights from a multi-center cohort study. Cardiovasc Diabetol. 2024;23:384. doi:10.1186/s12933-024-02476-9.
14. Savonitto G, Barbisan D, Ameri P, et al. Characteristics, Prognosis, and European Society of Cardiology and European Respiratory Society Risk Stratification in Patients With Obesity and Pulmonary Arterial Hypertension. Chest. 2025;168(3):749-62. doi:10.1016/j.chest.2025.04.008.
15. Sun Y, Sangam S, Guo Q, et al. Sex Differences, Estrogen Metabolism and Signaling in the Development of Pulmonary Arterial Hypertension. Front Cardiovasc Med. 2021;8:719058. doi:10.3389/fcvm.2021.719058.
16. Chen A, Zeng L, Yan Y, et al. Global pulmonary arterial hypertension trends and projections to 2046: a multi-method analysis of epidemiologic and demographic drivers using GBD 2021. J Thorac Dis. 2025;17(7):4420-38. doi:10.21037/jtd-2025-305.
17. Kovacs G, Olschewski H. The definition of pulmonary hypertension: history, practical implications and current controversies. Breathe. 2021;17(3):210076. doi:10.1183/20734735.0076-2021.
18. Fauvel C, Damy T, Berthelot E, et al. Post-capillary pulmonary hypertension in heart failure: impact of current definition in the PH-HF multicentre study. Eur Heart J. 2024;45(35):3274-88. doi:10.1093/eurheartj/ehae467.
19. Karia N, Howard L, Johnson M, et al. Predictors of outcomes in mild pulmonary hypertension according to 2022 ESC/ERS Guidelines: the EVIDENCE-PAH UK study. Eur Heart J. 2023;44(44):4678-91. doi:10.1093/eurheartj/ehad532.
20. Taran IN, Valieva ZS, Belevskaya AA, et al. Influence of demographic characteristics on the clinical course and results of therapy in patients with precapillary pulmonary hypertension. Terapevticheskii arkhiv. 2021;93(3):283-9. (In Russ.) doi:10.26442/00403660.2021.03.200655.
21. Lyapina IN, Valieva ZS, Martynyuk TV. Specific Therapy Strategy Choice for Patients With Pulmonary Arterial Hypertension and Inoperable Chronic Thromboembolic Pulmonary Hypertension: Switch or Escalate. Kardiologiia. 2025;65(1):50-7. (In Russ). doi:10.18087/cardio.2025.1.n2844.
22. Hoeper MM. Navigating Uncertainty in PAH Classification: Wedge Pressure Versus Disease Phenotypes. Circulation. 2025;152(1):4-6. doi:10.1161/CIRCULATIONAHA.125.073885.
23. Rosenkranz S, Hoeper MM, Maron BA. Pulmonary hypertension in heart failure: the good, the bad, and the ugly. Eur Heart J. 2024;45(35):3289-91. doi:10.1093/eurheartj/ehae518.
24. Rayner SG, Tedford RJ, Leary PJ, et al. "This patient needs a doctor, not a guideline!" The zone of uncertainty in pulmonary arterial wedge pressure measurement. Am J Respir Crit Care Med. 2024;210:712-14. doi:10.1164/rccm.202402-0359VP.
25. Preston IR, Howard LS, Langleben D, et al. Management of pulmonary hypertension in special conditions. Eur Respir J. 2024;64(4):2401180. doi:10.1183/13993003.01180-2024.
26. Hameed A, Condliffe R, Swift AJ, et al. Assessment of Right Ventricular Function-a State of the Art. Curr Heart Fail Rep. 2023;20(3):194-207. doi:10.1007/s11897-023-00600-6.
27. Lyapina IN, Teplova YuE, Martynyuk TV. Determinants of prognosis and management of patients with pulmonary hypertension due to left heart disease: a systematic review. Russian Journal of Cardiology. 2023;28(1S):5115. (In Russ). doi:10.15829/1560-4071-2023-5115.
28. Muraru D, Haugaa K, Donal E, et al. Right ventricular longitudinal strain in the clinical routine: a state-of-the-art review. Eur Heart J Cardiovasc Imaging. 2022;23(7):898-912. doi:10.1093/ehjci/jeac022.
29. Golukhova EZ, Slivneva IV, Mamalyga ML, et al. Right ventricular free-wall longitudinal speckle tracking strain as a prognostic criterion of adverse outcomes in patients with pulmonary hypertension: a systematic review and meta-analysis. Russian Journal of Cardiology. 2021;26(4):4417. (In Russ.) doi:10.15829/1560-4071-2021-4417. EDN: UKCCFC.
30. Belevskaya AA, Saidova MA, Martynyuk TV, et al. Heart remodeling and ventricular-arterial coupling in patients with IPAH and CTEPH. Russian Cardiology Bulletin. 2018;13(4):30-4. (In Russ.) doi:10.17116/Cardiobulletin20181304130.
31. Taran IN, Belevskaya AA, Saidova MA, et al. Initial Riociguat Monotherapy and Transition from Sildenafil to Riociguat in Patients with Idiopathic Pulmonary Arterial Hypertension: Influence on Right Heart Remodeling and Right Ventricular-Pulmonary Arterial Coupling. Lung. 2018;196(6):745-53. doi:10.1007/s00408-018-0160-4.
32. Baxan N, Zhao L, Ashek A, et al. Deep phenotyping the right ventricle to establish translational MRI biomarkers for characterization of adaptive and maladaptive states in pulmonary hypertension. Sci Rep. 2024;14(1):29774. doi:10.1038/s41598-024-79029-3.
33. Goncharova NS, Ryzhkov AV, Lapshin KB, et al. Cardiac magnetic resonance imaging in mortality risk stratification of patients with pulmonary hypertension. Russian Journal of Cardiology. 2023;28(9):5540. (In Russ.) doi:10.15829/15604071-2023-5540.
34. Rezukhina EA, Shariya MA, Martynyuk TV, et al. Non-invasive monitoring of specific therapy effectiveness in pulmonary arterial hypertension patients. Eurasian heart journal. 2025;(3):118-23. (In Russ.) doi:10.38109/2225-1685-2025-3-118-123.
35. Conde-Camacho R, Tuta-Quintero E, Bastidas-Goyes A, et al. Survival rates at one and five years for patients with group 1 pulmonary arterial hypertension at high altitude: A retrospective cohort study. Sci Prog. 2025;108(2):368504251336066. doi:10.1177/00368504251336066.
36. D’Alonzo GE, Barst RJ, Ayres SM, et al. Survival in patients with primary pulmonary hypertension: results from a national prospective registry. Ann Intern Med. 1991;115(5):343-9. doi:10.7326/0003-4819-115-5-343.
37. Avdeev SN, Barbarash OL, Bautin A, et al. 2020 Clinical practice guidelines for Pulmonary hypertension, including chronic thromboembolic pulmonary hypertension. Russian Journal of Cardiology. 2021;26(12):4683. (In Russ.) doi:10.15829/1560-4071-2021-4683.
38. Boucly A, Montani D, Bauer F, et al. Initial therapy in patients with pulmonary arterial hypertension and cardiovascular comorbidities. Eur Respir J. 2025;65(5):2400895. doi:10.1183/13993003.00895-2024.
39. Boucly A, Song S, Keles M, et al. Clustering Patients with Pulmonary Hypertension Using the Plasma Proteome. Am J Respir Crit Care Med. 2025;211(8):1492-503. doi:10.1164/rccm.202408-1574OC.
40. Humbert M, Guignabert C, Bonnet S, et al. Pathology and pathobiology of pulmonary hypertension: state of the art and research perspectives. Eur Respir J. 2019;53(1):1801887. doi:10.1183/13993003.01887-2018.
41. Guignabert C, Humbert M. Targeting transforming growth factor-β receptors in pulmonary hypertension. Eur Respir J. 2021;57(2):2002341. doi:10.1183/13993003.02341-2020.
42. Ryabkov VA, Vezikova NN, Goncharova NS, et al. Principles of healthcare management for patients with pulmonary hypertension: focus on continuity. Russian Journal of Cardiology. 2023;28(2):5335. (In Russ.) doi:10.15829/1560-4071-2023-5335.
- The increasing prevalence of pulmonary hypertension (PH) worldwide is associated with demographic changes, particularly the increasing elderly population proportion and lifestyle changes.
- Significant changes in the phenotype of patients with pulmonary arterial hypertension (PAH) are observed, which implies the importance of careful differential diagnosis of various PH forms using new approaches to patient phenotyping.
- The review outlines new trends in the development of personalized treatment approaches based on various phenotyping methods for patients with PH.
Review
For citations:
Lyapina I.N. A modern perspective on pulmonary hypertension phenotypes: a literature review. Russian Journal of Cardiology. 2025;30(2S):6701. (In Russ.) https://doi.org/10.15829/1560-4071-2025-6701. EDN: IUHKND
Views:
444
JATS XML
Email this article 