Introduction
In 2022, the European Society of Cardiology (ESC) and the European Respiratory Society (ERS) published a guideline on the 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 management of pulmonary arterial hypertension (PAH) and chronic thromboembolic pulmonary hypertension (CTEPH). ESC/ERS recommendations on the diagnosis and detection 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 detail, 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 >20 mmHg
- PAH is defined as pulmonary vascular resistance >2 WU, and pulmonary arterial wedge pressure (PAWP) of ≤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
- The 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 in 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).
Management of Pulmonary Arterial Hypertension
- Use clinical assessment, exercise tests, biochemical markers, echocardiography, and haemodynamic evaluations to evaluate disease severity and risk of death in patients with PAH
- Aim to achieve and maintain a low-risk profile with optimised medical therapy
- Use a three-tier model (low, intermediate, and high) for risk stratification at diagnosis; base on available data including haemodynamic evaluations
- Use a four-tier model (low, intermediate–low, intermediate–high, and high) for risk stratification during follow up; base on World Health Organization functional class, 6-minute walking distance, and brain natriuretic peptide/N-terminal pro-brain natriuretic peptide, plus additional factors if needed
- Consider therapy optimisation on an individual basis for patients with comorbidities and certain PAH aetiologies, bearing in mind that achieving a low-risk profile is not always possible.
General Measures for Patients with Pulmonary Arterial Hypertension
- The following are recommended for patients with PAH:
- supervised exercise training for patients on medical treatment
- psychosocial support
- immunisation against COVID-19, flu, and Streptococcus pneumoniae
- diuretic treatment for patients with signs of right ventricular failure and fluid retention
- correction of iron deficiency in patients with anaemia, with consideration to iron repletion in non-anaemic patients
- long-term oxygen therapy for patients whose arterial blood oxygen pressure is <8 kPa (60 mmHg) on at least two occasions
- in-flight oxygen administration for patients using oxygen or whose arterial blood oxygen pressure is <8 kPa (60 mmHg) at sea level
- multidisciplinary consultation at a specialist PH centre on occasions when anaesthesia is needed
- The following are not generally recommended for patients with PAH:
- anticoagulation, except on an individual basis
- angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, angiotensin receptor-neprilysin inhibitors, sodium–glucose cotransporter-2 inhibitors, beta-blockers, and ivabradine, unless required for comorbidities such as high blood pressure, coronary artery disease, left heart failure, or arrhythmias.
Pulmonary Arterial Hypertension in Women of Childbearing Potential
- Counsel at diagnosis about the potential risks of pregnancy
- Include advice against becoming pregnant
- Refer for psychological support if needed
- Provide tailored contraceptive advice, reinforcing the risks of contraceptive failure
- For women who consider pregnancy or who become pregnant, offer prompt counselling at an experienced PH centre covering:
- genetic counselling
- shared decision making
- psychological support for patients and families
- Pregnancy terminations should be carried out in specialist PH centres with psychological support for patients and families
- For women who want to have children, consider counselling on adoption or surrogacy with preconception genetic counselling
- Avoid endothelin receptor antagonists (ERAs) and riociguat in pregnancy due to their potential teratogenicity.
Pulmonary Arterial Hypertension with Signs of Capillary of Venous Involvement
- Use clinical and radiological findings, arterial blood gas analysis (ABG), pulmonary function tests (PFTs), and genetic testing to diagnose PAH with signs of venous and/or capillary involvement (pulmonary veno-occlusive disease (PVOD) or pulmonary capillary haemangiomatosis [PCH])
- Confirm heritable PVOD or PCH diagnosis by identifying biallelic EIF2AK4 mutations
- Refer eligible patients with PVOD or PCH to a transplant centre for evaluation as soon as they have been diagnosed
- Consider using drugs approved for PAH with careful monitoring of symptoms and gas exchange
- Do not use lung biopsy to confirm PVOD/PCH diagnosis.
Intensive Care Management of Patients with Pulmonary Arterial Hypertension
- When managing patients with right heart failure in intensive care:
- involve physicians who have relevant expertise
- treat causative factors
- use supportive measures, including inotropes and vasopressors, fluid management, and PAH drugs, as appropriate
- Consider mechanical circulatory support for selected patients as a bridge to transplantation or recovery; consider inter-hospital transfer if unavailable on site.
Management of Pulmonary Arterial Hypertension
Table 1: Recommendations for the Management of Patients with Pulmonary Arterial Hypertension| Patient Group | Recommendations |
|---|---|
| Vasoreactive Patients with IPAH, HPAH, or DPAH | |
| Patients with IPAH, HPAH, or DPAH who respond to acute vasoreactivity testing |
|
| Patients with IPAH, HPAH, or DPAH in WHO-FC I or II with marked haemodynamic improvement (mPAP <30 mmHg and PVR <4WU) on CCB treatment | Continue high dose CCBs |
| Patients who remain in WHO-FC III or IV, or those without marked haemodynamic improvement on high dose CCB treatment | Initiate PAH therapy |
| Patients with a positive vasoreactivity test but insufficient long-term response to CCBs who require additional PAH therapy | Consider continuation of CCB therapy |
| Do not prescribe CCBs for patients before a vasoreactivity study or for those who did not respond, except for other indications (e.g. Raynaud’s syndrome) | |
| Non-vasoreactive Patients with IPAH, HPAH, or DPAH Without Cardiopulmonary Comorbidities[A] | |
| Patients with IPAH, HPAH, or DPAH at high risk of death | Consider initial combination therapy with a PDE5i, an ERA, and IV/SC prostacyclin analogues |
| Patients with IPAH, HPAH, or DPAH at intermediate risk but with severe haemodynamic impairment, e.g. RAP ≥20 mmHg, CI <2.0 l/min/m2, SVI <31 ml/m2, and/or PVR ≥12 WU | Consider initial triple-combination therapy including IV/SC prostacyclin analogues |
| Patients with IPAH, HPAH, or DPAH at low or intermediate risk | Initial combination therapy with a PDE5i and an ERA is recommended |
| Initial oral drug combination therapy for patients with IPAH, HPAH, or DPAH without cardiopulmonary comorbidities |
|
| Follow-up patients with IPAH, HPAH, or DPAH at intermediate–low risk while receiving ERA/PDE5i therapy |
|
| Follow-up patients with IPAH, HPAH, or DPAH at intermediate–high or high risk while receiving ERA/PDE5i therapy |
|
| Sequential drug combination therapy for patients with IPAH, HPAH, or DPAH |
|
| Sequential drug combination therapy to reduce the risk of morbidity and mortality in patients with IPAH, HPAH, or DPAH |
|
| Sequential drug combination therapy to improve exercise capacity in patients with IPAH, HPAH, or DPAH |
|
| Sequential drug combination therapy to improve exercise capacity and/or alleviate PH symptoms in patients with IPAH, HPAH, or DPAH | Consider other sequential double- or triple-combination therapies |
| Non-vasoreactive Patients with IPAH, HPAH, or DPAH With Cardiopulmonary Comorbidities | |
| Patients with IPAH, HPAH, or DPAH and cardiopulmonary comorbidities | Consider initial monotherapy with a PDE5i or an ERA |
| Follow up patients with IPAH, HPAH, or DPAH with cardiopulmonary comorbidities at intermediate or high risk of death while receiving PDE5i or ERA monotherapy | Consider additional PAH medication on an individual basis |
| PAH Associated with Drugs or Toxins | |
| Patients exposed to relevant drugs or toxins in whom other causes of PH have been excluded | Diagnose drug- or toxin-associated PAH |
| Patients with suspected drug- or toxin-associated PAH | Immediately discontinue the causative agent if possible |
| Patients with intermediate- to high-risk PAH at diagnosis | Consider immediate PAH therapy |
| Patients with low-risk PAH |
|
| PAH Associated with Connective Tissue Disease or HIV | |
| Patients with PAH associated with CTD |
|
| Patients with PAH associated with HIV |
|
| PAH Associated with Portal Hypertension | |
| Patients with liver disease or portal hypertension with signs or symptoms suggestive of PH | Use echocardiography |
| Patients evaluated for liver transplantation or transjugular portosystemic shunt | Use echocardiography as a screening tool |
| Patients with PAH associated with portal hypertension |
|
| PAH Associated with Adult Congenital Heart Disease | |
| Patients with persistent PAH after defect closure | Risk assess |
| Patients with Eisenmenger syndrome |
|
| Patients with adult congenital heart disease, including Eisenmenger syndrome | Consider other ERAs, PDE5is, riociguat, prostacyclin analogues, and prostacyclin receptor agonists |
| Adults with congenital heart disease including Eisenmenger syndrome who do not meet treatment goals | Consider sequential combination therapy |
| Patients with Eisenmenger syndrome with pulmonary artery thrombosis without significant haemoptysis | Consider oral anticoagulant treatment |
| Women with Eisenmenger syndrome | Advise against pregnancy |
| Low- and intermediate-risk patients with PAH after corrected adult congenital heart disease | Consider initial oral combination therapy with PAH drugs |
| High-risk patients with PAH after corrected adult | Consider initial combination therapy including IV/SC prostacyclin analogues |
| Patients with iron deficiency | Consider supplemental iron treatment |
| Lung Transplantation | |
| Patients with an inadequate response to oral combination therapy, indicated by an intermediate–high or high risk or a REVEAL risk score >7 | Refer potentially eligible candidates for lung transplant evaluation |
| Patients with a high risk of death or a REVEAL risk score ≥10, despite receiving optimised medical therapy including SC or IV prostacyclin analogues | List patients for lung transplantation |
| Shunt Closure in Patients with Pulmonary–Systemic Flow Ratio >1.5:1 Based on Calculated Pulmonary Vascular Resistance[B] | |
| Patients with an ASD, VSD, or PDA and PVR <3 WU | Shunt closure is recommended |
| Patients with an ASD, VSD, or PDA and PVR 3–5 WU | Consider shunt closure |
| Patients with an ASD and PVR >5 WU that reduces to <5 WU with PAH treatment | Consider shunt closure |
| Patients with a VSD or PDA and PVR >5 WU | Consider shunt closure after careful evaluation in a specialised centre |
| Patients with an ASD and PVR >5 WU, despite PAH treatment | Shunt closure is not recommended |
| [A] Cardiopulmonary comorbidities mostly occur in elderly patients and include risk factors for heart failure with preserved ejection fraction, such as obesity, diabetes, coronary heart disease, a history of hypertension, and/or a low DLCO [B] Do not make decisions about shunt closure based solely on haemodynamic numbers—follow a multiparametric strategyIPAH=idiopathic pulmonary arterial hypertension; HPAH=heritable pulmonary arterial hypertension; DPAH=drug- or toxin-associated pulmonary arterial hypertension; CCB=calcium channel blocker; RHC=right heart catheterisation; WHO-FC=World Health Organization functional class; mPAP=mean pulmonary arterial pressure; PVR=pulmonary vascular resistance; PAH=pulmonary arterial hypertension; WU=wood units; PDE5i=phosphodiesterase 5 inhibitor; ERA=endothelin receptor antagonist; IV=intravenous; SC=subcutaneous; CTD=connective tissue disease; RAP=right atrial pressure; CI=cardiac index; SVI=stroke volume index; PH=pulmonary hypertension; HIV=human immunodeficiency virus; CTD=connective tissue disease; CO=cardiac output; REVEAL=registry to evaluate early and long-term pulmonary arterial hypertension disease management; ASD=atrial septal defect; VSD=ventricular septal defect; PDA=patent ductus arteriosus; DLCO=lung diffusion capacity for carbon monoxide | |
Pulmonary Hypertension Associated with Left Heart Disease
Treatment of Pulmonary Hypertension Associated with Left Heart Disease
- Optimise treatment of the underlying condition before assessing suspected PH
- PAH drugs are not recommended for patients with PH associated with left heart disease (LHD) due to safety concerns identified when ERAs were used in patients with heart failure (HF) and when sildenafil was used in patients with persistent PH after valvular heart disease correction
- Monitor patients who have PH and multiple risk factors for LHD, normal PAWP at rest but an abnormal response to exercise or fluid challenge if they are treated with PAH drugs
- Do not use phosphodiesterase-5 inhibitors (PDE5is) for patients with HF with preserved ejection fraction and isolated post-capillary PH
Table 2: Recommended Options for Patients with Pulmonary Hypertension Associated with Left Heart Disease
| Patient Group | Recommendations |
|---|---|
| Suspected PH in patients with LHD | RHC is recommended if it aids management decisions |
| Patients with severe tricuspid regurgitation with or without LHD before surgical or interventional valve repair | RHC is recommend |
| Patients with LHD and suspected PH with features of a severe pre-capillary component and/or RV dysfunction markers | Refer to a PH centre for a diagnosis |
| Patients with LHD CpcPH with a severe pre-capillary component (e.g. PVR >5 WU) | Follow an individualised approach to treatment |
| Patients with PH at RHC, a borderline PAWP (13–15 mmHg) and features of HFpEF | Consider additional testing with exercise or fluid challenge to uncover post-capillary PH |
| PH=pulmonary hypertension; LHD=left heart disease; RHC=right heart catheterisation; RV=right ventricular; CpcPH=combined post- and pre-capillary pulmonary hypertension; PVR=pulmonary vascular resistance; PAWP=pulmonary arterial wedge pressure; HFpEF=heart failure with preserved ejection fraction | |
Pulmonary Hypertension Associated with Lung Disease and/or Hypoxia
Assessment and Management of Patients with Pulmonary Hypertension
- For patients with lung disease and suspected PH:
- perform echocardiography and interpret results together with ABG, PFTs (including lung diffusion capacity for carbon monoxide), and CT imaging
- perform echocardiography assessments when the patient is clinically stable, as exacerbations can significantly raise pulmonary artery pressure
- perform RHC if the results are expected to aid management decisions
- optimise treatment of underlying lung disease and any hypoxaemia, sleep-disordered breathing, or alveolar hypoventilation
- Refer to a PH centre in the following cases (unless patient has end-stage lung disease and is not a lung transplant candidate):
- patients with lung disease and suspected severe PH
- when there is uncertainty regarding PH treatment.
| Patient Group | Recommendations |
| Patients with lung disease and severe PH | Adopt an individualised treatment approach |
| Eligible patients with lung disease and PH | Refer for lung transplantation evaluation |
| Patients with PH associated with ILD | Consider inhaled treprostinil |
| Patients with severe PH associated with ILD | Consider PDE5is only with individual decision-making in PH centres |
Do not use:
| |
| PH=pulmonary hypertension; ILD=interstitial lung disease; PDE5i=phosphodiesterase 5 inhibitor; IPF=idiopathic pulmonary fibrosis; IIP=idiopathic interstitial pneumonia; PAH=pulmonary arterial hypertension | |
Management of Chronic Thromboembolic Pulmonary Hypertension and Chronic Thromboembolic Pulmonary Disease Without Pulmonary Hypertension
Table 4: Treatment Recommendations for Patients with Chronic Thromboembolic Pulmonary Hypertension or Chronic Thromboembolic Pulmonary Disease| Patient Group | Recommendations |
| CTEPH | |
| Patients with CTEPH |
|
| Patients with CTEPH and antiphospholipid syndrome | Anticoagulation with VKAs |
| Patients with CTEPH and fibrotic obstructions within pulmonary arteries accessible by surgery | Treat with PEA |
| Patients who are technically inoperable or have residual PH after PEA and distal obstructions amenable to BPA | BPA is recommended |
| Symptomatic patients with inoperable CTEPH or persistent/recurrent PH after PEA | Treat with riociguat |
| Patients with persistent PH after PEA and patients with inoperable CTEPH | Consider a multimodal approach |
| Patients in WHO-FC III–IV with inoperable CTEPH or persistent/recurrent PH after PEA | Consider SC treprostinil |
| Symptomatic patients with inoperable CTEPH | Consider off-label use of drugs approved for PAH |
| Patients with inoperable CTEPH | Consider a combination of sGC stimulator/PDE5i, ERA, or parenteral prostacyclin analogues |
| Technically operable patients with a high proportion of distal disease and an unfavourable risk–benefit ratio for PEA | Consider BPA |
| Patients with CTEPH who are candidates for BPA | Consider medical therapy before BPA |
Patients with CTEPH:
| Offer long-term follow up |
| CTEPD without PH | |
| Patients with CTEPD without PH | Consider long-term anticoagulant therapy on an individual basis when risk of PE recurrence is intermediate or high, or there is no history of venous thromboembolism |
| Symptomatic patients with CTEPD without PH | Consider PEA or BPA for selected patients |
| CTEPH=chronic thromboembolic pulmonary hypertension; VKA=vitamin K antagonist; PEA=pulmonary endarterectomy; PH=pulmonary hypertension; BPA=balloon pulmonary angioplasty; WHO-FC=World Health Organization functional class; SC=subcutaneous; PAH=pulmonary arterial hypertension; sGC=soluble guanylate cyclase; PDE5i=phosphodiesterase 5 inhibitor; ERA=endothelin receptor antagonist; CTEPD=chronic thromboembolic pulmonary disease; PE=pulmonary embolism | |
References
References