How does Pulmonary Arterial Hypertension (PAH) develop?

The exact causes behind the development of pulmonary arterial hypertension (PAH) remain unknown. However, research has led to a better understanding of the underlying pathological mechanisms.

What is PAH?

©Janssen-Cilag NV - EM-38436 - 21-jul-2020 - vu/er Luc Van Oevelen, Antwerpseweg 15-17, 2340 Beerse, ©Janssen-Cilag B.V. - EM-38436 - 21-jul-2020

Classification of PH
PAH subtypes

The 2015 European Society of Cardiology and European Respiratory Society (ESC/ERS) guidelines classify pulmonary hypertension (PH) into five main groups, according to their similar clinical presentation, pathological findings, haemodynamic characteristics and treatment strategy.[1]

PAH-Explained-Pathophysiology - Classification of PAH

Adapted from Galiè et al. 2016[1]

These 5 PH groups are further subcategorised. [1]

1. PAH 

1.1 Idiopathic 
1.2 Heritable
1.2.1 Bone morphogenetic protein receptor type 2 (BMPR2) mutation
1.2.2 Other mutations
1.3 Drug- and toxin-induced
1.4 Associated with:
1.4.1 Connective tissue disease
 1.4.2 Human immunodeficiency virus (HIV) infection
1.4.3 Portal hypertension
1.4.4 Congenital heart disease
1.4.5 Schistosomiasis

1'. Pulmonary veno-occlusive disease and/or pulmonary capillary haemangiomatosis

1’.1 Idiopathic
1’.2 Heritable
1’.2.1 Eukaryotic translation initiation factor 2 alpha kinase 4 (EIF2AK4) mutation
1’.2.2 Other mutations
1’.3 Drug-, toxin- and radiation-induced
1’.4 Associated with:
1’.4.1 Connective tissue disease
1’.4.2 HIV infection

1”. Persistent pulmonary hypertension of the newborn

2. PH due to left heart disease

2.1 Left ventricular systolic dysfunction
2.2 Left ventricular diastolic dysfunction
2.3 Valvular disease
2.4 Congenital/acquired left heart inflow/outflow tract obstruction and congenital cardiomyopathies
2.5 Congenital/acquired pulmonary veins stenosis

3. Pulmonary hypertension due to lung diseases and/or hypoxia

3.1 Chronic obstructive pulmonary disease
3.2 Interstitial lung disease
3.3 Other pulmonary diseases with mixed restrictive and obstructive pattern
3.4 Sleep-disordered breathing
3.5 Alveolar hypoventilation disorders
3.6 Chronic exposure to high altitude
3.7 Developmental lung diseases

4. Chronic thromboembolic pulmonary hypertension and other pulmonary artery obstructions

4.1 Chronic thromboembolic pulmonary hypertension
4.2 Other pulmonary artery obstructions
4.2.1 Angiosarcoma
4.2.2 Other intravascular tumours
4.2.3 Arteritis
4.2.4 Congenital pulmonary arteries stenoses
4.2.5 Parasites (hydatidosis)

5. Pulmonary hypertension with unclear and/or multifactorial mechanisms

5.1 Haematological disorders: chronic haemolytic anaemia, myeloproliferative disorders, splenectomy
5.2 Systemic disorders: sarcoidosis, pulmonary histiocytosis, lymphangioleiomyomatosis, neurofibromatosis
5.3 Metabolic disorders: glycogen storage disease, Gaucher disease, thyroid disorders
5.4 Others: pulmonary tumoural thrombotic microangiopathy, fibrosing mediastinitis, chronic renal failure (with/without dialysis), segmental pulmonary hypertension

You may also be interested in

Diagnosis of PAH

Clinical guidelines set out the diagnostic pathway so patients can be referred and treated as quickly as possible. 

Treatment of PAH

Modern treatments can significantly improve patients’ symptoms and slow the rate of clinical deterioration. 

Contact us, we're happy to help

Do you have a question for us or did you not find what you were looking for? Let us know and one of our Janssen-specialists will contact you as soon as possible.

Discover our products

Discover Janssen's portfolio and the matching SmPC's.

Look at 3D clinical images

On this page you will find interactive 3D animations of the human anatomy and various syndromes. This allows you to zoom in on the anatomy, tissue structures, disease mechanisms and the course of the disease.


Galiè N et al. Eur Heart J 2016; 37:67–119.
Lau E et al. Nat Rev Cardiol 2017; 14:603–614.
Ma L, Chung WK. J Pathol 2017; 241:273–280.
Montani D et al. Eur Respir Rev 2013; 22:244–250.
Prins KW, Thenappan T. Cardiol Clin 2016; 34:363v374.
Thakkar V, Lau EMT. Best Pract Res Clin Rheumatol 2016; 30:22–38.
Kiely DG et al. Eur Heart J 2019; 21:K9–20.
Teng R, Wu T. J Formos Med Assoc 2013; 112:177–184.
Badesch DB et al. Chest 2010; 137:376–387.
D’Alonzo GE et al. Ann Intern Med 1991; 115:343–349.
Hoeper MM et al. Int J Cardiol 2016; 203:612–613.
Barst R et al. Chest 2013; 144:160–168.
Montani D et al. Orphanet J Rare Dis 2013; 8:97.
Hoeper MM, Gibbs JSR. Eur Respir Rev 2014; 23:450–457.
Rhee RL et al. Am J Respir Crit Care 2015; 192:1111–1117.
Kolstad KD et al. Chest 2018; 154:862–871.
McGoon MD, Miller DP. Eur Respir Rev 2012; 21:8–18.
Health and Social Care Information Centre. National Audit of Pulmonary Hypertension, 2013. Available at: https://files.digital.nhs.uk/publicationimport/pub13xxx/pub13318/nati-pulm-hype-audi-2013-rep.pdf (last accessed May 2020).
Montani D et al. Orphanet J Rare Dis 2013; 8:97.
Galiè N et al. Eur Heart J 2010; 31:2080–2086.
Vonk Noordegraaf A et al. J Am Coll Cardiol 2013; 62:D22–33.
Galiè N et al. Eur Heart J 2010; 31:2080–2086.
Jonigk D et al. Am J Pathol 2011; 179:167–179.
Jonigk D et al. Am J Pathol 2011; 179:167–179.
Gaine S. JAMA 2000; 284:3160–3168.
Humbert M et al. Eur Respir Rev 2012; 21:306–312.
CP-192318 - November 2020