In 2022, the European Society of Cardiology (ESC) and the European Respiratory Society (ERS) published a guideline on the diagnosis and treatment of pulmonary hypertension (PH).
This specialist Guidelines overview for secondary care cardiologists covers a selection of the recommendations from the guideline, with particular focus on the classification, diagnosis, and detection of pulmonary arterial hypertension (PAH) and chronic thromboembolic pulmonary hypertension (CTEPH). ESC/ERS recommendations on the management of PAH and CTEPH can be found in a separate Guidelines summary.
This overview does not cover diagnosis and treatment of PH in children, which is performed in specialist centres. Refer to the full guideline for the complete set of recommendations on paediatric PH.
All of the recommendations, strength of recommendations, rationale, further details, and background information can be found in the full ESC/ERS guideline.
For a summary of the recommendations relevant to primary care settings, see the separate Guidelines primary care summary.
Key Takeaways from the Guideline
- The 2022 guideline has an emphasis on diagnosing and treating PAH and CTEPH
- The haemodynamic definition of PH has been amended to a mean pulmonary arterial pressure (mPAP) >20 mmHg
- PAH is defined as pulmonary vascular resistance >2 WU, and pulmonary arterial wedge pressure ≤15 mmHg
- The main diagnostic algorithm for PH (which can be viewed in the full guideline) consists of a three-step approach:
- suspicion by first-line physicians
- detection by echocardiography
- confirmation with right heart catheterisation (RHC) in PH centres
- High-risk or complex patients should be rapidly referred to PH centres
- Screening strategies are recommended for PAH in patients with scleroderma and in patients at risk of heritable PAH to shorten the time from symptom onset to diagnosis of PAH
- To improve under-diagnosis of CTEPH, enhanced recognition of computed tomography (CT) and echocardiographic signs at the time of acute pulmonary embolism (PE), along with a systematic follow-up of patients with acute PE, are recommended
- Criteria for echocardiographic and cardiac magnetic resonance imaging have been added to the risk-stratification table, refining non-invasive evaluation at diagnosis
- The intermediate-risk patient group is further subdivided into intermediate–low risk or intermediate–high risk, creating a four-strata risk stratification
- A PAH treatment algorithm (which can be viewed in the full guideline) highlights the importance of cardiopulmonary comorbidities, risk assessment—both at diagnosis and follow-up—and the importance of combination therapies
- Paediatric diagnosis, treatment, and follow-up strategies can be based on adult recommendations but adapted for age, risk stratification, and treatment response
- Patients with chronic thromboembolic pulmonary disease may not have PH, and further research is called for in this area
- The treatment algorithm for CTEPH (which can be viewed in the full guideline) has been modified, and includes multimodal therapy with surgery, drugs, and balloon pulmonary angioplasty
- Supervised exercise training is now recommended for patients with PAH under medical therapy.
Clinical Classification of Pulmonary Hypertension
- PH is broadly classified into the following groups:
- group 1: PAH
- group 2: PH associated with left heart disease
- group 3: PH associated with lung diseases and/or hypoxia
- group 4: PH associated with pulmonary artery obstructions
- group 5: PH with unclear and/or multifactorial mechanisms (refer to the full guideline for further information).
- Raise early suspicion of PH and ensure that patients with a high probability of PAH, CTEPH, or other types of severe PH are rapidly referred to specialist PH centres
- Identify underlying diseases (particularly left heart disease and lung disease) and comorbidities to facilitate effective classification, risk assessment, and treatment.
- Use echocardiography as the first-line test for suspected PH
- Assess the probability of PH based on abnormal tricuspid regurgitation velocity (TRV) and other echocardiographic signs including:
- right or left ventricle basal diameter/area ratio >1.0
- interventricular septum flattening (left ventricle eccentricity index >1.1 in systole and/or diastole)
- tricuspid annular plane systolic excursion/systolic PAP ratio <0.55 mm/mmHg
- right ventricular outflow tract acceleration time <105 ms and/or mid-systolic notching
- early diastolic pulmonary regurgitation velocity >2.2 m/s
- pulmonary artery diameter > aortic root diameter
- pulmonary artery diameter >25 mm
- inferior vena cava diameter >21 mm, with decreased inspiratory collapse (<50% with a sniff, or <20% with quiet inspiration)
- right atrium area (end-systole) >18 cm2
- Maintain the current TRV threshold (>2.8 m/s) for echocardiographic probability of PH, in line with the updated haemodynamic definition
- Consider further testing based on the probability of PH, as determined by echocardiography and the patient’s symptoms, risk factors, and presence of conditions associated with PAH or CTEPH
- Consider cardiopulmonary exercise testing to further determine the likelihood of PH in symptomatic patients with intermediate echocardiographic probability of PH.
Imaging and Other Diagnostic Tests
- Perform pulmonary function tests with lung diffusion capacity for carbon monoxide in the initial evaluation of patients with PH
- Open or thoracoscopic lung biopsy should be avoided in patients with PAH
- Assess for CTEPH in patients with unexplained PH with perfusion or ventilation/perfusion lung scanning
- Include CT pulmonary angiography in the work-up for patients with suspected CTEPH
- Identify any associated conditions in patients with PAH through routine biochemistry, haematology, immunology, HIV, and thyroid function tests
- Use abdominal ultrasound to check for portal hypertension
- Consider chest CT for all patients with PH
- Consider digital subtraction angiography for patients with CTEPH.
Right Heart Catheterisation and Vasoreactivity Testing
- RHC and vasoreactivity testing should be done in specialist PH centres
- Perform RHC to confirm PH diagnosis (particularly PAH or CTEPH) and inform treatment decisions
- RHC should follow standardised protocols and involve a complete set of haemodynamics
- Perform vasoreactivity testing for patients with idiopathic, heritable, or drug-associated PAH to identify acute vasoresponders suitable for high-dose calcium channel blockers (CCBs)
- do not use vasoreactivity to assess suitability for CCBs in PAH patients other than those with idiopathic, heritable, or drug-associated PAH, and in PH groups 2–5
- preferably, use inhaled nitric oxide or inhaled iloprost
- IV epoprostenol can be used, but testing takes longer
- a positive acute response is a reduction in mPAP ≥10 mmHg to reach an absolute value ≤40 mmHg, with increased or unchanged cardiac output
- also test patients with a baseline mPAP ≤40 mmHg; the same responder criteria apply.
Table 1: Typical Patient Profiles Presenting with Pulmonary Hypertension
|Group 1: Pulmonary Arterial Hypertension||Group 2: Pulmonary Hypertension Associated with Left Heart Disease||Group 3: Pulmonary Hypertension Associated with Lung Diseases and/or Hypoxia||Group 4: Pulmonary Hypertension Associated with Pulmonary Artery Obstructions|
|Presentation||Variable and depends on associated conditions||History and clinical findings indicating LHD|
|Hypoxaemia Needing Oxygen||UncommonA||Uncommon||Common and can be severe||Uncommon, except in severe PH with distal occlusion of PA|
|PFT and Spirometry||Normal or mild impairment||Normal or mild impairment||Abnormal, as per underlying lung disease||Normal or mild impairment|
|DLCO||Normal or mild-to-moderate reductionB||Normal or mild-to-moderate reduction, particularly in patients with HFpEF||Often very low (<45% predicted)||Normal or mild-to-moderate reduction|
|ABG: PaCO2||Low||Normal||Low, normal, or high||Low-to-normal|
|Lung Scintigraphy||Normal or matched||Normal or matched||Normal or matched||Mismatched perfusion defect|
|Chest CT||Signs of PH or PVOD|
|CPET: VE/VCO2 slope||High||Mildly elevated||Mildly elevated||High|
|CPET: PETCO2||Low, decreasing on exertion||Normal, increasing on exertion||Normal, increasing on exertion||Low, decreasing on exertion|
|RHC||Pre-capillary PH||Post-capillary PH||Pre-capillary PH||Pre- or post-capillary PH|
|AExcept for conditions with low DLCO or right-to-left shunting|
BDLCO can be low in SSc-PAH, PVOD, and some types of IPAH
HFpEF=heart failure with preserved ejection fraction; LHD=left heart disease; CTEPH=chronic thromboembolic pulmonary hypertension; VTE=venous thromboembolism; PH=pulmonary hypertension; PA=pulmonary artery; RA=right atrium; RV=right ventricle; LA=left atrium; LV=left ventricle; PFT=pulmonary function test; DLCO=lung diffusion capacity for carbon monoxide; ABG=arterial blood gas analysis; PaO2=partial pressure of arterial oxygen; PaCO2=partial pressure of arterial carbon dioxide; sPAP=systolic pulmonary arterial pressure; LHD=left heart disease; HF=heart failure; CT=computed tomography; PVOD=pulmonary veno-occlusive disease; CPET=cardiopulmonary exercise testing; VE/VCO2=ventilatory equivalent for carbon dioxide; PETCO2=end-tidal partial pressure of carbon dioxide; EOV=exercise oscillatory ventilation; RHC=right heart catheterization; SSc-PAH=systemic sclerosis-associated pulmonary arterial hypertension; IPAH=idiopathic pulmonary arterial hypertension
|Adapted from Table 14, Characteristic diagnostic features of patients with different forms of pulmonary hypertension, from 2022 ESC/ERS Guidelines for the diagnosis and treatment of pulmonary hypertension|