Pulmonary hypertension (PH) is a disorder of the pulmonary circulation defined by an elevated mean pulmonary arterial pressure (mPAP) > 20 mmHg at rest, measured by right heart catheterisation. The underlying pathophysiology is that of progressive pulmonary vascular remodelling and subsequent right ventricular dysfunction and failure.
Pulmonary hypertension can be found in several clinical conditions that are classified in 5 clinical groups based on similar pathophysiological mechanisms, haemodynamics and therapeutic management (see table below).
Left heart disease is the most common cause of pulmonary hypertension, followed by lung disease and the treatment focus on optimisation of the underlying heart and lung conditions.
Rare forms of pulmonary hypertension, such as pulmonary arterial hypertension (PAH) and chronic thromboembolic pulmonary hypertension (CTEPH), required specialist input and, when suspected, should be promptly referred to a PH centre to avoid worse outcomes as a result of delays in initiating treatment.
GROUP 1 - Pulmonary arterial hypertension (PAH)
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- 1.1 Idiopathic
- 1.2 Heritable
- 1.3 Associated with drugs and toxins
- 1.4 Associated with:
- 1.4.1 Connective tissue disease
- 1.4.2 HIV infection
- 1.4.3 Portal hypertension
- 1.4.4 Congenital heart disease
- 1.4.5 Schistosomiasis
- 1.5 PAH with features of venous/capillary (PVOD/PCH) involvement
GROUP 2 - PH associated with left heart disease
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- 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
- 2.1 Heart failure:
GROUP 3 - PH associated with lung diseases and/or hypoxia
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- 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
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- 4.1 Chronic thrombo-embolic PH
- 4.2 Other pulmonary artery obstructions
GROUP 5 - PH with unclear and/or multifactorial mechanisms
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- 5.1 Haematological disorders (myeloproliferative disorders)
- 5.2 Systemic disorders (Sarcoidosis, Langerhans’ cell histiocytosis)
- 5.3 Metabolic disorders (glycogen storage diseases)
- 5.4 Chronic renal failure with or without haemodialysis
- 5.5 Pulmonary tumour thrombotic microangiopathy
- 5.6 Fibrosing mediastinitis
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Suggestive Symptoms |
Associated risk factors |
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Fatigue |
Systemic sclerosis/connective tissue disease* |
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Exertional dyspnoea |
Advanced liver disease |
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Syncope/presyncope |
Congenital heart disease |
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Peripheral oedema |
Family history of PAH |
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Atypical chest pain |
HIV infection |
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Palpitations |
Known history of venous thromboembolism |
*For patients with systemic sclerosis, we recommend using the DETECT screening algorithm. This is based on a multicentre multinational screening study (Coghlan et al Ann Rheum Dis 2014 Jul;73(7):1340-9).
Suggested investigations prior to referral:
- Echocardiogram
- CT pulmonary angiography or ventilation/perfusion scan
- Full lung function tests
- Pulse oximetry at rest +/- arterial blood gases
- Full blood count, Renal and liver function tests, Autoantibody screen
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Echocardiography should be used as the primary imaging modality in patients with unexplained breathlessness and suspected pulmonary hypertension, with signs suggestive of PH including: |
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Peak tricuspid regurgitation velocity > 2.8 m/s |
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Evidence of significant right ventricular dilation or dysfunction |
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Absence of left ventricular systolic/diastolic dysfunction, left atrial dilatation or significant mitral or aortic valve disease |
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Patients with intermediate to high probability of pulmonary hypertension on echocardiogram AND risk factors or associated conditions for PAH or CTEPH should be promptly referred to a National Pulmonary Hypertension specialist centre such as our Pulmonary Vascular Diseases Unit (PVDU) at Royal Papworth Hospital
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We encourage you to promptly refer any patient aged older than 16 whom you believe has:
- Unexplained pulmonary hypertension
- Suspected Group 1 Pulmonary arterial hypertension (see causes above)
- Chronic thromboembolic pulmonary disease
- Miscellaneous/uncertain causes (i.e. sarcoidosis, myeloproliferative disease)
We consider referrals for patients with or left heart or lung disease (specially ILD), with high probability of pulmonary hypertension and impaired right ventricular function that appears out of proportion to the severity of cardiac/pulmonary disease.
Urgent referral/case discussion: Contact Pulmonary hypertension Consultant on-call - via hospital switchboard (01223 638000)
Non urgent: Send an email to: papworth.phreferrals@nhs.net
Please include full medical history and list of medications plus copies of investigations full reports. Where possible we would prefer advanced imaging to be sent either via an electronic image link or on CD.
Who to refer
The PVDU encourages you to promptly refer any patient aged over 16 who you believe has:
- Unexplained pulmonary hypertension
- Pulmonary arterial hypertension (see causes above)
- Chronic thromboembolic pulmonary hypertension
- Miscellaneous causes of pulmonary hypertension
- Patients with PH associated to left heart disease and/or lung disease are reviewed on an individual basis.
Echocardiography should be used as the primary screening modality, with pulmonary hypertension being suggested by:
- Estimated pulmonary artery systolic pressure of ≥ 40mmHg + RA pressure (Tricuspid regurgitant jet velocity of 2-8-3.4m/s)
- Evidence of significant right ventricular dilation or dysfunction
- Absence of left ventricular dysfunction
For patients with systemic sclerosis we recommend using the DETECT screening tool. A link to the online calculator is here, but Android and Apple apps are available for your phone. This is based on a multicentre multinational screening study.
When referring, please include:
- Full patient history and current medications
- Name of referring consultant with contact details
Suggested investigations prior to referral:
- Full lung function tests
- Echocardiography with full report
- Pulse oximetry at rest +/- arterial blood gases
- HIV, renal and liver function tests
- Autoantibody screen
- Consider ventilation/perfusion scan or CT pulmonary angiography
Please include copies of any radiological investigations and reports. Where possible we would prefer advanced imaging to be sent either via an electronic image link or on CD.
How to refer a new patient
Non urgent
Please email papworth.phreferrals@nhs.net
Urgent referral/case discussion
Pulmonary hypertension consultant on-call: via hospital switchboard
Royal Papworth Hospital NHS Foundation Trust
Papworth Road
Cambridgeshire Biomedical Campus
Cambridge
CB2 0AY
Phone: 01223 638000
A printable copy of these referral guidelines is available online.
Management and follow-up of pulmonary hypertension patients
Typically we follow-up patients every 3-6 months. Since many patients are referred from a long distance, we ask that they remain under the joint care of the GP, local hospital consultant and the local pulmonary hypertension service. We are seeking to develop shared care of patients requiring long-term follow-up with interested physicians (in place with Coventry University Hospital, at University Hospitals Coventry & Warwickshire, Derriford Hospital at Plymouth and Norfolk and Norwich Hospital at Norwich). Please contact us for more details. We will be happy to discuss individual patient follow-up with you.
Pulmonary arterial hypertension targeted therapies used:
Over the past 10 years there have been a number of treatments licensed for pulmonary arterial hypertension. These drugs are backed up with clinical trial evidence to support their use. The Royal Papworth PVDU is responsible for the prescription and delivery of the pulmonary arterial hypertension targeted drugs but the general practioner remains responsible for the prescription of any other drugs the patient is taking. Patients and healthcare professionals are to contact us for advice 24 hours a day, 365 days a year.
Phosphodiesterase type 5 inhibitors (Sildenafil, Tadalafil)
Usually first line treatment. Sildenafil is taken three times per day and tadalafil once daily. Common side effects include flushing, headache, systemic hypotension, nasal stuffiness, epistaxis and gastro-oesophageal reflux. It can rarely cause non-arteritic anterior ischaemic optic neuropathy (need to discontinue if sudden visual disturbance occurs).
Endothelin receptor antagonists (Bosentan, Ambrisentan and Macitentan)
Bosentan is taken twice daily whereas Ambrisentan and Macitentan are taken once daily. Common side effects include: flushing, headache, systemic hypotension, ankle oedema, anaemia and abnormal LFTs (ALT, AST). In view of the side effect patients are required to have their haemoglobin checked monthly for the first month and then three-monthly and LFTs checked monthly.
Prostenoids (nebulised Iloprost, intravenous Epoprostenol)
Prostenoid treaments used in patients with more advanced pulmonary hypertension and require educating the patient and relatives about how to make up and use the treatments.
Nebulised Iloprost is given through a special nebuliser rather than the standard nebuliser used for bronchodilators. The drug has a short half-life and therefore needs to be inhaled every three hours (seven times per day). Common side effects include: flushing, headache, jaw ache, cough, wheezing, systemic hypotension and diarrhoea.
Continuous intravenous Epoprostenol is given via a Hickman line using a pump. The drug has a very short half-life (3-5 minutes) and therefore cannot be stopped abruptly. Patients and relatives are given extensive training and support when initiated on Epoprostenol. Prior to discharge they are assessed to ensure they are competent to manage the infusion and what to if they have any problems. Common side effects include: headache, flushing, jaw ache, diarrhoea, nausea and sepsis related to Hickman line.