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Summary for secondary care

Guideline Essentials: 2022 ESC/ERS Recommendations on the Management of Pulmonary Hypertension in Secondary Care


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).
See the separate Guidelines summary on the diagnosis and detection of PH for a breakdown of the diagnostic features associated with each classification.

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 GroupRecommendations
Vasoreactive Patients with IPAH, HPAH, or DPAH
Patients with IPAH, HPAH, or DPAH who respond to acute vasoreactivity testing
  • High-dose CCBs
  • Close follow up with complete reassessment after 3–4 months of therapy (including RHC)
Patients with IPAH, HPAH, or DPAH in WHO-FC I or II with marked haemodynamic improvement (mPAP <30 mmHg and PVR <4WU) on CCB treatmentContinue high dose CCBs
Patients who remain in WHO-FC III or IV, or those without marked haemodynamic improvement on high dose CCB treatmentInitiate PAH therapy
Patients with a positive vasoreactivity test but insufficient long-term response to CCBs who require additional PAH therapyConsider 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 deathConsider 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 WUConsider 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
  • Recommended initial combinations:
    • ambrisentan and tadalafil
    • macitentan and tadalafil
  • Consider initial combination therapy with other ERAs and PDE5is
Follow-up patients with IPAH, HPAH, or DPAH at intermediate–low risk while receiving ERA/PDE5i therapy
  • Consider adding selexipag at follow up
  • Consider switching from PDE5i to riociguat at follow up
Follow-up patients with IPAH, HPAH, or DPAH at intermediate–high or high risk while receiving ERA/PDE5i therapy
  • Consider adding IV/SC prostacyclin analogues at follow up
  • Consider referring for lung transplant evaluation
Sequential drug combination therapy for patients with IPAH, HPAH, or DPAH
  • Base treatment escalations on risk assessment and general treatment strategies
  • Do not combine riociguat with PDE5is
Sequential drug combination therapy to reduce the risk of morbidity and mortality in patients with IPAH, HPAH, or DPAH
  • Add macitentan to PDE5is or oral/inhaled prostacyclin analogues
  • Add selexipag to ERAs and/or PDE5is (ERAs used in the GRIPHON study were bosentan and ambrisentan)
  • Add oral treprostinil to ERA or PDE5i/riociguat monotherapy
  • Do not add bosentan to sildenafil to reduce the risk of morbidity and mortality events
Sequential drug combination therapy to improve exercise capacity in patients with IPAH, HPAH, or DPAH
  • Add sildenafil to epoprostenol
  • Consider adding:
    • inhaled treprostinil to sildenafil or bosentan monotherapy
    • riociguat to bosentan
    • tadalafil to bosentan
    • inhaled iloprost to bosentan
    • ambrisentan to sildenafil
    • bosentan to sildenafil
    • sildenafil to bosentan
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 comorbiditiesConsider 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 monotherapyConsider 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 excludedDiagnose drug- or toxin-associated PAH
Patients with suspected drug- or toxin-associated PAHImmediately discontinue the causative agent if possible
Patients with intermediate- to high-risk PAH at diagnosisConsider immediate PAH therapy
Patients with low-risk PAH
  • Re-evaluate 3–4 months after discontinuing suspected drug or toxin
  • Consider PAH therapy if haemodynamics have not normalised
PAH Associated with Connective Tissue Disease or HIV
Patients with PAH associated with CTD
  • Treat underlying condition according to current guidelines
  • Treat PAH as per patients with IPAH
Patients with PAH associated with HIV
  • Continue antiretroviral treatment according to current guidelines
  • Consider initial monotherapy followed by sequential combination if necessary, taking comorbidities and drug interactions into account
PAH Associated with Portal Hypertension
Patients with liver disease or portal hypertension with signs or symptoms suggestive of PHUse echocardiography
Patients evaluated for liver transplantation or transjugular portosystemic shuntUse echocardiography as a screening tool
Patients with PAH associated with portal hypertension
  • Refer to centres with expertise in managing both conditions
  • Consider initial monotherapy followed by sequential combinations if needed, taking account of underlying liver disease and liver transplantation indications
  • Consider liver transplantation on an individual basis if PVR is normal or near normal with PAH therapy
  • Do not prescribe PAH drugs for patients with portal hypertension and unclassified PH (elevated mPAP, high CO, and a normal PVR)
PAH Associated with Adult Congenital Heart Disease
Patients with persistent PAH after defect closureRisk assess 
Patients with Eisenmenger syndrome
  • Risk assess
  • Consider supplemental oxygen therapy if it reduces symptoms and consistently increases arterial oxygen saturation
  • Do not use phlebotomy to lower elevated haematocrit
  • Bosentan is recommended in symptomatic patients to improve exercise capacity
Patients with adult congenital heart disease, including Eisenmenger syndromeConsider other ERAs, PDE5is, riociguat, prostacyclin analogues, and prostacyclin receptor agonists 
Adults with congenital heart disease including Eisenmenger syndrome who do not meet treatment goalsConsider sequential combination therapy
Patients with Eisenmenger syndrome with pulmonary artery thrombosis without significant haemoptysisConsider oral anticoagulant treatment 
Women with Eisenmenger syndromeAdvise against pregnancy
Low- and intermediate-risk patients with PAH after corrected adult congenital heart diseaseConsider initial oral combination therapy with PAH drugs 
High-risk patients with PAH after corrected adultConsider initial combination therapy including IV/SC prostacyclin analogues
Patients with iron deficiencyConsider 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 >7Refer 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 analoguesList 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 WUShunt closure is recommended
Patients with an ASD, VSD, or PDA and PVR 3–5 WUConsider shunt closure
Patients with an ASD and PVR >5 WU that reduces to <5 WU with PAH treatmentConsider shunt closure
Patients with a VSD or PDA and PVR >5 WUConsider shunt closure after careful evaluation in a specialised centre
Patients with an ASD and PVR >5 WU, despite PAH treatmentShunt 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
See Table 2 for further recommendations in specific cases of PH with LHD.

Table 2: Recommended Options for Patients with Pulmonary Hypertension Associated with Left Heart Disease

Patient GroupRecommendations
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 HFpEFConsider 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.
Table 3: Treatment for Patients with Pulmonary Arterial Hypertension Associated with Lung Disease and/or Hypoxia
Patient GroupRecommendations
Patients with lung disease and severe PHAdopt an individualised treatment approach
Eligible patients with lung disease and PHRefer for lung transplantation evaluation
Patients with PH associated with ILDConsider inhaled treprostinil
Patients with severe PH associated with ILDConsider PDE5is only with individual decision-making in PH centres
Do not use:
  • PDE5is for patients with ILD and non-severe PH
  • ambrisentan for patients with PH associated with IPF
  • riociguat for patients with PH associated with IIP
  • PAH medication for patients with lung disease and non-severe PH (except inhaled treprostinil which may be considered for patients with PH associated with ILD, irrespective of PH severity)
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 GroupRecommendations
Patients with CTEPH
  • Test for antiphospholipid syndrome
  • Prescribe lifelong therapeutic doses of anticoagulation
  • Review patients with a CTEPH team for multimodality management assessment
Patients with CTEPH and antiphospholipid syndromeAnticoagulation with VKAs
Patients with CTEPH and fibrotic obstructions within pulmonary arteries accessible by surgeryTreat with PEA
Patients who are technically inoperable or have residual PH after PEA and distal obstructions amenable to BPABPA is recommended
Symptomatic patients with inoperable CTEPH or persistent/recurrent PH after PEATreat with riociguat
Patients with persistent PH after PEA and patients with inoperable CTEPHConsider a multimodal approach
Patients in WHO-FC III–IV with inoperable CTEPH or persistent/recurrent PH after PEAConsider SC treprostinil
Symptomatic patients with inoperable CTEPHConsider off-label use of drugs approved for PAH
Patients with inoperable CTEPHConsider 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 PEAConsider BPA
Patients with CTEPH who are candidates for BPAConsider medical therapy before BPA
Patients with CTEPH:
  • established on medical therapy 
  • who have had PEA or BPA 
Offer long-term follow up
CTEPD without PH
Patients with CTEPD without PHConsider 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 PHConsider 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