An overview of the clinical classification of pulmonary hypertension (PH), with associated conditions and important investigations to consider
| Group 1 Pulmonary arterial hypertension (PAH) | |
| 1.1 Idiopathic PAH | |
| 1.1.1 Non-responders at vasoreactivity testing | Important to exclude alternative causes of PAH before assigning this diagnosis |
| 1.1.2 Acute responders at vasoreactivity testing | Diagnosed during vasoreactivity testing at RHC: • mPAP reduction of ≥10 mmHg (to <40 mmHg) • Cardiac output is increased/maintained |
| 1.2 Heritable PAH | Enquire regarding family history of PAH • Offer genetic counselling and consider gene panel • e.g. gene mutations in BMPR2, EIF2AK4, TBX4, ACVRL1, ENG [6] |
| 1.3 Associated with drugs and toxins | Enquire regarding specific drug and toxin exposure at home and at work (e.g. aminorex, fenfluramine, methamphetamines) |
| 1.4 Associated with: | |
| 1.4.1 Connective tissue disease (CTD) | CTDs associated with PAH include SSc-PAH, SLE, mixed CTD, rheumatoid arthritis, dermatomyositis, Sjögren syndrome [3] Considerations for subjects with SSc and suspected PAH: • Ask regarding symptoms of Raynaud's, GORD, etc. • Examine for features such as digital ulcers, sclerodactyly, calcinosis, telangiectasia, microstomia; consider nailfold capillaroscopy • Request serum ANA and CTD panel • Exclude comorbid LHD, and ILD in suspected SSc-PAH |
| 1.4.2 HIV infection | Assess for infection with HIV |
| 1.4.3 Portal hypertension | Portal hypertension with or without cirrhosis is associated with PAH Investigate with: • Liver screen including autoimmune serology, viral hepatitis screen and HIV • Doppler ultrasound of liver and portal system • A hepatic venous pressure gradient >5 mmHg during invasive catheterisation (may be normal in subjects with extrahepatic portal hypertension) |
| 1.4.4 Congenital heart disease | Eisenmenger syndrome; PAH associated with prevalent systemic-to-pulmonary shunts, PAH-with small/coincidental defects, PAH after defect correction [3, 7] Consider investigation with: • Doppler and contrast echocardiography • Cardiac MRI • Stepwise assessment of oxygen saturations at RHC if left-to-right shunt suspected |
| 1.4.5 Schistosomiasis | Present in 5% of patients with hepatosplenic schistosomiasis infection Consider investigation with: • Confirm infection, e.g. through the detection of parasite eggs in the stool or urine • Doppler ultrasound of liver and portal system to assess for portal hypertension |
| 1.5 PAH with features of venous/capillary (PVOD/PCH) involvement | Consider family history, medical history (e.g. prior chemotherapy), occupational exposures (e.g. organic solvents) Consider genetic screening for EIF2AK4 Suspect if: • Often accompanied by severe hypoxia and marked reductions in DLCO (<50%) • Treatment with PAH specific therapy may be complicated by pulmonary oedema • CT thorax: septal lines, centrilobular ground-glass opacities, mediastinal adenopathy |
| 1.6 Persistent PH of the newborn | Failed circulatory adaptation at birth with sustained elevation in PVR; diagnosed in neonates and often resolves |
| Group 2 PH associated with left heart disease | |
| Consider the pre-test probability of LHD and ensure adequate imaging of left heart, such as echocardiography, cardiac MRI. If suspected, consider fluid challenge at RHC [2, 8]. | |
| 2.1 Heart failure: | |
| 2.1.1 With preserved ejection fraction | |
| 2.1.2 With reduced or mildly reduced ejection fraction | |
| 2.2 Valvular heart disease | |
| 2.3 Congenital/acquired cardiovascular conditions leading to post-capillary PH | |
| Group 3 PH associated with lung diseases and/or hypoxia | |
| Investigate with ABG, PFTs, chest imaging such as high-resolution CT thorax, polysomnography. | |
| 3.1 Obstructive lung disease or emphysema | |
| 3.2 Restrictive lung disease | |
| 3.3 Lung disease with mixed restrictive/obstructive pattern | |
| 3.4 Hypoventilation syndromes | |
| 3.5 Hypoxia without lung disease (e.g. high altitude) | |
| 3.6 Developmental lung disorders | |
| Group 4 PH associated with pulmonary artery obstructions | |
| CTPA and Vʹ/Qʹ imaging are important investigations. Consider invasive pulmonary angiogram if Group 4 PH suspected. | |
| 4.1 Chronic thromboembolic PH | |
| 4.2 Other pulmonary artery obstructions | |
| Group 5 PH with unclear and/or multifactorial mechanisms | |
| Guided by individual history and assessment. | |
| 5.1 Haematological disorders | |
| 5.2 Systemic disorders | |
| 5.3 Metabolic disorders | |
| 5.4 Chronic renal failure with or without haemodialysis | |
| 5.5 Pulmonary tumour thrombotic microangiopathy | |
| 5.6 Fibrosing mediastinitis | |
RHC: right heart catheterisation; mPAP: mean pulmonary artery pressure; BMPR2: bone morphogenetic protein receptor type 2; EIF2AK4: eukaryotic translation initiation factor 2 alpha kinase 4; TBX4: T-box 4; ACVRL1: activin receptor-like kinase 1 (ALK1); ENG: endoglin; SSc: systemic sclerosis; SLE: systemic lupus erythematosus; GORD: gastro-oesophageal reflux disease; ANA: antinuclear antibody; LHD: left heart disease; ILD: interstitial lung disease; MRI: magnetic resonance imaging; PVOD: pulmonary veno-occlusive disease; PCH: pulmonary capillary haemangiomatosis; DLCO: diffusion capacity of the lung for carbon monoxide; CT: computed tomography; PVR: pulmonary vascular resistance; ABG: arterial blood gas; PFTs: pulmonary function tests; CTPA: computed tomography pulmonary angiogram; Vʹ/Qʹ: ventilation/perfusion. Reproduced and modified from [2], with permission.